1  5572 84 ROLE OF MICRORNA IN DIABETIC CARDIOMYOPATHY: FROM MECHANISM TO INTERVENTION. DIABETIC CARDIOMYOPATHY IS A CHRONIC AND IRREVERSIBLE HEART COMPLICATION IN DIABETIC PATIENTS, AND IS CHARACTERIZED BY COMPLEX PATHOPHYSIOLOGIC EVENTS INCLUDING EARLY DIASTOLIC DYSFUNCTION, CARDIAC HYPERTROPHY, VENTRICULAR DILATION AND SYSTOLIC DYSFUNCTION, EVENTUALLY RESULTING IN HEART FAILURE. DESPITE THESE CHARACTERISTICS, THE UNDERLYING MECHANISMS LEADING TO DIABETIC CARDIOMYOPATHY ARE STILL ELUSIVE. RECENT STUDIES HAVE IMPLICATED MICRORNA, A SMALL AND HIGHLY CONSERVED NON-CODING RNA MOLECULE, IN THE ETIOLOGY OF DIABETES AND ITS COMPLICATIONS, SUGGESTING A POTENTIALLY NOVEL APPROACH FOR THE DIAGNOSIS AND TREATMENT OF DIABETIC CARDIOMYOPATHY. THIS BRIEF REVIEW AIMS AT CAPTURING RECENT STUDIES RELATED TO THE ROLE OF MICRORNA IN DIABETIC CARDIOMYOPATHY. THIS ARTICLE IS PART OF A SPECIAL ISSUE ENTITLED: GENETIC AND EPIGENETIC CONTROL OF HEART FAILURE - EDITED BY JUN REN & MEGAN YINGMEI ZHANG.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
2  4191 30 METABOLIC LANDSCAPE IN CARDIAC AGING: INSIGHTS INTO MOLECULAR BIOLOGY AND THERAPEUTIC IMPLICATIONS. CARDIAC AGING IS EVIDENT BY A REDUCTION IN FUNCTION WHICH SUBSEQUENTLY CONTRIBUTES TO HEART FAILURE. THE METABOLIC MICROENVIRONMENT HAS BEEN IDENTIFIED AS A HALLMARK OF MALIGNANCY, BUT RECENT STUDIES HAVE SHED LIGHT ON ITS ROLE IN CARDIOVASCULAR DISEASES (CVDS). VARIOUS METABOLIC PATHWAYS IN CARDIOMYOCYTES AND NONCARDIOMYOCYTES DETERMINE CELLULAR SENESCENCE IN THE AGING HEART. METABOLIC ALTERATION IS A COMMON PROCESS THROUGHOUT CARDIAC DEGENERATION. IMPORTANTLY, THE INVOLVEMENT OF CELLULAR SENESCENCE IN CARDIAC INJURIES, INCLUDING HEART FAILURE AND MYOCARDIAL ISCHEMIA AND INFARCTION, HAS BEEN REPORTED. HOWEVER, METABOLIC COMPLEXITY AMONG HUMAN AGING HEARTS HINDERS THE DEVELOPMENT OF STRATEGIES THAT TARGETS METABOLIC SUSCEPTIBILITY. ADVANCES OVER THE PAST DECADE HAVE LINKED CELLULAR SENESCENCE AND FUNCTION WITH THEIR METABOLIC REPROGRAMMING PATHWAY IN CARDIAC AGING, INCLUDING AUTOPHAGY, OXIDATIVE STRESS, EPIGENETIC MODIFICATIONS, CHRONIC INFLAMMATION, AND MYOCYTE SYSTOLIC PHENOTYPE REGULATION. IN ADDITION, METABOLIC STATUS IS INVOLVED IN CRUCIAL ASPECTS OF MYOCARDIAL BIOLOGY, FROM FIBROSIS TO HYPERTROPHY AND CHRONIC INFLAMMATION. HOWEVER, FURTHER ELUCIDATION OF THE METABOLISM INVOLVEMENT IN CARDIAC DEGENERATION IS STILL NEEDED. THUS, DECIPHERING THE MECHANISMS UNDERLYING HOW METABOLIC REPROGRAMMING IMPACTS CARDIAC AGING IS THOUGHT TO CONTRIBUTE TO THE NOVEL INTERVENTIONS TO PROTECT OR EVEN RESTORE CARDIAC FUNCTION IN AGING HEARTS. HERE, WE SUMMARIZE EMERGING CONCEPTS ABOUT METABOLIC LANDSCAPES OF CARDIAC AGING, WITH SPECIFIC FOCUSES ON WHY METABOLIC PROFILE ALTERS DURING CARDIAC DEGENERATION AND HOW WE COULD UTILIZE THE CURRENT KNOWLEDGE TO IMPROVE THE MANAGEMENT OF CARDIAC AGING.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
3   245 25 ADRENERGIC REPRESSION OF THE EPIGENETIC READER MECP2 FACILITATES CARDIAC ADAPTATION IN CHRONIC HEART FAILURE. RATIONALE: IN CHRONIC HEART FAILURE, INCREASED ADRENERGIC ACTIVATION CONTRIBUTES TO STRUCTURAL REMODELING AND ALTERED GENE EXPRESSION. ALTHOUGH ADRENERGIC SIGNALING ALTERS HISTONE MODIFICATIONS, IT IS UNKNOWN, WHETHER IT ALSO AFFECTS OTHER EPIGENETIC PROCESSES, INCLUDING DNA METHYLATION AND ITS RECOGNITION. OBJECTIVE: THE AIM OF THIS STUDY WAS TO IDENTIFY THE MECHANISM OF REGULATION OF THE METHYL-CPG-BINDING PROTEIN 2 (MECP2) AND ITS FUNCTIONAL SIGNIFICANCE DURING CARDIAC PRESSURE OVERLOAD AND UNLOADING. METHODS AND RESULTS: MECP2 WAS IDENTIFIED AS A REVERSIBLY REPRESSED GENE IN MOUSE HEARTS AFTER TRANSVERSE AORTIC CONSTRICTION AND WAS NORMALIZED AFTER REMOVAL OF THE CONSTRICTION. SIMILARLY, MECP2 REPRESSION IN HUMAN FAILING HEARTS RESOLVED AFTER UNLOADING BY A LEFT VENTRICULAR ASSIST DEVICE. THE CLUSTER MIR-212/132 WAS UPREGULATED AFTER TRANSVERSE AORTIC CONSTRICTION OR ON ACTIVATION OF ALPHA1- AND BETA1-ADRENOCEPTORS AND MIR-212/132 LED TO REPRESSION OF MECP2. PREVENTION OF MECP2 REPRESSION BY A CARDIOMYOCYTE-SPECIFIC, DOXYCYCLINE-REGULATABLE TRANSGENIC MOUSE MODEL AGGRAVATED CARDIAC HYPERTROPHY, FIBROSIS, AND CONTRACTILE DYSFUNCTION AFTER TRANSVERSE AORTIC CONSTRICTION. ABLATION OF MECP2 IN CARDIOMYOCYTES FACILITATED RECOVERY OF FAILING HEARTS AFTER REVERSIBLE TRANSVERSE AORTIC CONSTRICTION. GENOME-WIDE EXPRESSION ANALYSIS, CHROMATIN IMMUNOPRECIPITATION EXPERIMENTS, AND DNA METHYLATION ANALYSIS IDENTIFIED MITOCHONDRIAL GENES AND THEIR TRANSCRIPTIONAL REGULATORS AS MECP2 TARGET GENES. COINCIDENT WITH ITS REPRESSION, MECP2 WAS REMOVED FROM ITS TARGET GENES, WHEREAS DNA METHYLATION OF MECP2 TARGET GENES REMAINED STABLE DURING PRESSURE OVERLOAD. CONCLUSIONS: THESE DATA CONNECT ADRENERGIC ACTIVATION WITH A MICRORNA-MECP2 EPIGENETIC PATHWAY THAT IS IMPORTANT FOR CARDIAC ADAPTATION DURING THE DEVELOPMENT AND RECOVERY FROM HEART FAILURE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                             
4  2554 29 EPIGENETICS IN REACTIVE AND REPARATIVE CARDIAC FIBROGENESIS: THE PROMISE OF EPIGENETIC THERAPY. EPIGENETIC CHANGES PLAY A PIVOTAL ROLE IN THE DEVELOPMENT OF A WIDE SPECTRUM OF HUMAN DISEASES INCLUDING CARDIOVASCULAR DISEASES, CANCER, DIABETES, AND INTELLECTUAL DISABILITIES. CARDIAC FIBROGENESIS IS A COMMON PATHOPHYSIOLOGICAL PROCESS SEEN DURING CHRONIC AND STRESS-INDUCED ACCELERATED CARDIAC AGING. WHILE ADEQUATE PRODUCTION OF EXTRACELLULAR MATRIX (ECM) PROTEINS IS NECESSARY FOR POST-INJURY WOUND HEALING, EXCESSIVE SYNTHESIS AND ACCUMULATION OF EXTRACELLULAR MATRIX PROTEIN IN THE STRESSED OR INJURED HEARTS CAUSES DECREASED OR LOSS OF LUSITROPY THAT LEADS TO CARDIAC FAILURE. THIS SELF-PERPETUATING DEPOSITION OF COLLAGEN AND OTHER MATRIX PROTEINS EVENTUALLY ALTER CELLULAR HOMEOSTASIS; IMPAIR TISSUE ELASTICITY AND LEADS TO MULTI-ORGAN FAILURE, AS SEEN DURING PATHOGENESIS OF CARDIOVASCULAR DISEASES, CHRONIC KIDNEY DISEASES, CIRRHOSIS, IDIOPATHIC PULMONARY FIBROSIS, AND SCLERODERMA. IN THE LAST 25 YEARS, MULTIPLE STUDIES HAVE INVESTIGATED THE MOLECULAR BASIS OF ORGAN FIBROSIS AND HIGHLIGHTED ITS MULTI-FACTORIAL GENETIC, EPIGENETIC, AND ENVIRONMENTAL REGULATION. IN THIS MINIREVIEW, WE FOCUS ON FIVE MAJOR EPIGENETIC REGULATORS AND DISCUSS THEIR CENTRAL ROLE IN CARDIAC FIBROGENESIS. ADDITIONALLY, WE COMPARE AND CONTRAST THE EPIGENETIC REGULATION OF HYPERTENSION-INDUCED REACTIVE FIBROGENESIS AND MYOCARDIAL INFARCTION-INDUCED REPARATIVE OR REPLACEMENT CARDIAC FIBROGENESIS. AS MICRORNAS-ONE OF THE MAJOR EPIGENETIC REGULATORS-CIRCULATE IN PLASMA, WE ALSO ADVOCATE THEIR POTENTIAL DIAGNOSTIC ROLE IN CARDIAC FIBROSIS. LASTLY, WE DISCUSS THE EVOLUTION OF NOVEL EPIGENETIC-REGULATING DRUGS AND PREDICT THEIR CLINICAL ROLE IN THE SUPPRESSION OF PATHOLOGICAL CARDIAC REMODELING, CARDIAC AGING, AND HEART FAILURE. J. CELL. PHYSIOL. 232: 1941-1956, 2017. (C) 2016 WILEY PERIODICALS, INC.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
5  3064 28 GENOME-WIDE DNA METHYLATION ENCODES CARDIAC TRANSCRIPTIONAL REPROGRAMMING IN HUMAN ISCHEMIC HEART FAILURE. ISCHEMIC CARDIOMYOPATHY (ICM) IS THE CLINICAL ENDPOINT OF CORONARY HEART DISEASE AND A LEADING CAUSE OF HEART FAILURE. DESPITE GROWING DEMANDS TO DEVELOP PERSONALIZED APPROACHES TO TREAT ICM, PROGRESS IS LIMITED BY INADEQUATE KNOWLEDGE OF ITS PATHOGENESIS. SINCE EPIGENETICS HAS BEEN IMPLICATED IN THE DEVELOPMENT OF OTHER CHRONIC DISEASES, THE CURRENT STUDY WAS DESIGNED TO DETERMINE WHETHER TRANSCRIPTIONAL AND/OR EPIGENETIC CHANGES ARE SUFFICIENT TO DISTINGUISH ICM FROM OTHER ETIOLOGIES OF HEART FAILURE. SPECIFICALLY, WE HYPOTHESIZE THAT GENOME-WIDE DNA METHYLATION ENCODES TRANSCRIPTIONAL REPROGRAMMING IN ICM. RNA-SEQUENCING ANALYSIS WAS PERFORMED ON HUMAN ISCHEMIC LEFT VENTRICULAR TISSUE OBTAINED FROM PATIENTS WITH END-STAGE HEART FAILURE, WHICH ENRICHED KNOWN TARGETS OF THE POLYCOMB METHYLTRANSFERASE EZH2 COMPARED TO NON-ISCHEMIC HEARTS. COMBINED RNA SEQUENCING AND GENOME-WIDE DNA METHYLATION ANALYSIS REVEALED A ROBUST GENE EXPRESSION PATTERN CONSISTENT WITH SUPPRESSION OF OXIDATIVE METABOLISM, INDUCED ANAEROBIC GLYCOLYSIS, AND ALTERED CELLULAR REMODELING. LASTLY, KLF15 WAS IDENTIFIED AS A PUTATIVE UPSTREAM REGULATOR OF METABOLIC GENE EXPRESSION THAT WAS ITSELF REGULATED BY EZH2 IN A SET DOMAIN-DEPENDENT MANNER. OUR OBSERVATIONS THEREFORE DEFINE A NOVEL ROLE OF DNA METHYLATION IN THE METABOLIC REPROGRAMMING OF ICM. FURTHERMORE, WE IDENTIFY EZH2 AS AN EPIGENETIC REGULATOR OF KLF15 ALONG WITH DNA HYPERMETHYLATION, AND WE PROPOSE A NOVEL MECHANISM THROUGH WHICH CORONARY HEART DISEASE REPROGRAMS THE EXPRESSION OF BOTH INTERMEDIATE ENZYMES AND UPSTREAM REGULATORS OF CARDIAC METABOLISM SUCH AS KLF15.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
6  6357 31 THE ROLE OF HYPERGLYCAEMIA IN THE DEVELOPMENT OF DIABETIC CARDIOMYOPATHY. DIABETES MELLITUS IS A METABOLIC DISORDER WITH A CHRONIC HYPERGLYCAEMIC STATE. CARDIOVASCULAR DISEASES ARE THE PRIMARY CAUSE OF MORTALITY IN PATIENTS WITH DIABETES. INCREASING EVIDENCE SUPPORTS THE EXISTENCE OF DIABETIC CARDIOMYOPATHY, A CARDIAC DYSFUNCTION WITH IMPAIRED CARDIAC CONTRACTION AND RELAXATION, INDEPENDENT OF CORONARY AND/OR VALVULAR COMPLICATIONS. DIABETIC CARDIOMYOPATHY CAN LEAD TO HEART FAILURE. SEVERAL PRECLINICAL AND CLINICAL STUDIES HAVE AIMED TO DECIPHER THE UNDERLYING MECHANISMS OF DIABETIC CARDIOMYOPATHY. AMONG ALL THE CO-FACTORS, HYPERGLYCAEMIA SEEMS TO PLAY AN IMPORTANT ROLE IN THIS PATHOLOGY. HYPERGLYCAEMIA HAS BEEN SHOWN TO ALTER CARDIAC METABOLISM AND FUNCTION THROUGH SEVERAL DELETERIOUS MECHANISMS, SUCH AS OXIDATIVE STRESS, INFLAMMATION, ACCUMULATION OF ADVANCED GLYCATED END-PRODUCTS AND UPREGULATION OF THE HEXOSAMINE BIOSYNTHESIS PATHWAY. THESE MECHANISMS ARE RESPONSIBLE FOR THE ACTIVATION OF HYPERTROPHIC PATHWAYS, EPIGENETIC MODIFICATIONS, MITOCHONDRIAL DYSFUNCTION, CELL APOPTOSIS, FIBROSIS AND CALCIUM MISHANDLING, LEADING TO CARDIAC STIFFNESS, AS WELL AS CONTRACTILE AND RELAXATION DYSFUNCTION. THIS REVIEW AIMS TO DESCRIBE THE HYPERGLYCAEMIC-INDUCED ALTERATIONS THAT PARTICIPATE IN DIABETIC CARDIOMYOPATHY, AND THEIR CORRELATION WITH THE SEVERITY OF THE DISEASE AND PATIENT MORTALITY, AND TO PROVIDE AN OVERVIEW OF CARDIAC OUTCOMES OF GLUCOSE-LOWERING THERAPY.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
7  1468 22 DISTINCT EPIGENETIC PROGRAMS REGULATE CARDIAC MYOCYTE DEVELOPMENT AND DISEASE IN THE HUMAN HEART IN VIVO. EPIGENETIC MECHANISMS AND TRANSCRIPTION FACTOR NETWORKS ESSENTIAL FOR DIFFERENTIATION OF CARDIAC MYOCYTES HAVE BEEN UNCOVERED. HOWEVER, RESHAPING OF THE EPIGENOME OF THESE TERMINALLY DIFFERENTIATED CELLS DURING FETAL DEVELOPMENT, POSTNATAL MATURATION, AND IN DISEASE REMAINS UNKNOWN. HERE, WE INVESTIGATE THE DYNAMICS OF THE CARDIAC MYOCYTE EPIGENOME DURING DEVELOPMENT AND IN CHRONIC HEART FAILURE. WE FIND THAT PRENATAL DEVELOPMENT AND POSTNATAL MATURATION ARE CHARACTERIZED BY A COOPERATION OF ACTIVE CPG METHYLATION AND HISTONE MARKS AT CIS-REGULATORY AND GENIC REGIONS TO SHAPE THE CARDIAC MYOCYTE TRANSCRIPTOME. IN CONTRAST, PATHOLOGICAL GENE EXPRESSION IN TERMINAL HEART FAILURE IS ACCOMPANIED BY CHANGES IN ACTIVE HISTONE MARKS WITHOUT MAJOR ALTERATIONS IN CPG METHYLATION AND REPRESSIVE CHROMATIN MARKS. NOTABLY, CIS-REGULATORY REGIONS IN CARDIAC MYOCYTES ARE SIGNIFICANTLY ENRICHED FOR CARDIOVASCULAR DISEASE-ASSOCIATED VARIANTS. THIS STUDY UNCOVERS DISTINCT LAYERS OF EPIGENETIC REGULATION NOT ONLY DURING PRENATAL DEVELOPMENT AND POSTNATAL MATURATION BUT ALSO IN DISEASED HUMAN CARDIAC MYOCYTES.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
8  2314 25 EPIGENETIC REGULATION OF ENDOTHELIAL-TO-MESENCHYMAL TRANSITION IN CHRONIC HEART DISEASE. ENDOTHELIAL-TO-MESENCHYMAL TRANSITION (ENDMT) IS A PROCESS IN WHICH ENDOTHELIAL CELLS LOSE THEIR PROPERTIES AND TRANSFORM INTO FIBROBLAST-LIKE CELLS. THIS TRANSITION PROCESS CONTRIBUTES TO CARDIAC FIBROSIS, A COMMON FEATURE OF PATIENTS WITH CHRONIC HEART FAILURE. TO DATE, NO SPECIFIC THERAPIES TO HALT OR REVERSE CARDIAC FIBROSIS ARE AVAILABLE, SO KNOWLEDGE OF THE UNDERLYING MECHANISMS OF CARDIAC FIBROSIS IS URGENTLY NEEDED. IN ADDITION, ENDMT CONTRIBUTES TO OTHER CARDIOVASCULAR PATHOLOGIES SUCH AS ATHEROSCLEROSIS AND PULMONARY HYPERTENSION, BUT ALSO TO CANCER AND ORGAN FIBROSIS. REMARKABLY, THE MOLECULAR MECHANISMS DRIVING ENDMT ARE LARGELY UNKNOWN. EPIGENETICS PLAY AN IMPORTANT ROLE IN REGULATING GENE TRANSCRIPTION AND TRANSLATION AND HAVE BEEN IMPLICATED IN THE ENDMT PROCESS. THEREFORE, EPIGENETICS MIGHT BE THE MISSING LINK IN UNRAVELING THE UNDERLYING MECHANISMS OF ENDMT. HERE, WE REVIEW THE INVOLVEMENT OF EPIGENETIC REGULATORS DURING ENDMT IN THE CONTEXT OF CARDIAC FIBROSIS. THE ROLE OF DNA METHYLATION, HISTONE MODIFICATIONS (ACETYLATION AND METHYLATION), AND NONCODING RNAS (MICRORNAS, LONG NONCODING RNAS, AND CIRCULAR RNAS) IN THE FACILITATION AND INHIBITION OF ENDMT ARE DISCUSSED, AND POTENTIAL THERAPEUTIC EPIGENETIC TARGETS WILL BE HIGHLIGHTED.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
9   246 33 ADULT STEM CELL THERAPY FOR CARDIAC REPAIR IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION LEADING TO ISCHEMIC HEART FAILURE: AN OVERVIEW OF EVIDENCE FROM THE RECENT CLINICAL TRIALS. BACKGROUND: CARDIOVASCULAR DISEASES (CVD) STILL REPRESENT THE LEADING CAUSE OF MORTALITY WORLDWIDE, DESPITE THE REMARKABLE ADVANCES IN INTERVENTIONAL CARDIOLOGY, CARDIAC SURGERY, AND MODERN PHARMACOTHERAPY, PARTICULARLY IN THE SETTING OF ACUTE MYOCARDIAL INFARCTION (AMI), CHRONIC ISCHEMIC HEART FAILURE (HF), CARDIOMYOPATHY (CM), AND THE ASSOCIATED LEFT VENTRICULAR (LV) DYSFUNCTION. A SIGNIFICANT LOSS OF CARDIOMYOCYTES THAT UNDERLIES ALL OF THESE CONDITIONS WAS PREVIOUSLY CONSIDERED IRREVERSIBLE. HOWEVER, CURRENT EVIDENCE INDICATES THAT THE HUMAN HEART HAS SOME POTENTIAL FOR REPAIR, AND OVER THE PAST DECADE, MANY RESEARCH STUDIES HAVE BEEN EXPLORING THE USE OF STEM CELLS (SCS) TO FACILITATE RESTORATION OF MYOCARDIUM. CONSEQUENTLY, THE SAFETY, FEASIBILITY, AND EFFECTIVENESS OF SC THERAPY HAVE BEEN REPORTED IN MANY RANDOMIZED CLINICAL TRIALS (RCTS), USING DIFFERENT LINEAGES OF ADULT SCS. NEVERTHELESS, THE CLINICAL BENEFITS OF SC THERAPY ARE NOT YET WELL ESTABLISHED. IN THE NEAR FUTURE, UNDERSTANDING OF THE COMPLEX INTERRELATIONS BETWEEN SCS, PARACRINE FACTORS, GENETIC OR EPIGENETIC PREDISPOSITIONS, AND MYOCARDIAL MICROENVIRONMENT, IN THE CONTEXT OF AN INDIVIDUAL PATIENT, WILL BE CRUCIAL FOR TRANSLATION OF THIS KNOWLEDGE INTO PRACTICAL DEVELOPMENT OF SUCCESSFUL, LONG-TERM REGENERATIVE SC THERAPEUTIC APPLICATIONS, IN A GROWING POPULATION OF PATIENTS SUFFERING FROM PREVIOUS MYOCARDIAL INFARCTION (MI) LEADING TO CHRONIC ISCHEMIC CARDIOMYOPATHY. CONCLUSION: THIS OVERVIEW HIGHLIGHTS THE THERAPEUTIC POTENTIAL OF ADULT SCS IN TERMS OF THEIR POSSIBLE REGENERATIVE CAPACITY, SAFETY, AND CLINICAL OUTCOMES, IN PATIENTS WITH AMI, AND/OR SUBSEQUENT HF (DUE TO CHRONIC ISCHEMIC CARDIOMYOPATHY). THIS REVIEW WAS BASED UPON PUBMED DATABASE SEARCH FOR TRIALS ON SC THERAPY, IN PATIENTS WITH AMI AND HF, AND THE MAIN TIMEFRAME WAS SET FROM 2006 TO 2016.	2017	
                                                                                                                                                                                                                                                                                                                            
10  1015 24 CIGARETTE SMOKING CAUSES EPIGENETIC CHANGES ASSOCIATED WITH CARDIORENAL FIBROSIS. CLINICAL STUDIES INDICATE THAT SMOKING COMBUSTIBLE CIGARETTES PROMOTES PROGRESSION OF RENAL AND CARDIAC INJURY, LEADING TO FUNCTIONAL DECLINE IN THE SETTING OF CHRONIC KIDNEY DISEASE (CKD). HOWEVER, BASIC STUDIES USING IN VIVO SMALL ANIMAL MODELS THAT MIMIC CLINICAL PATHOLOGY OF CKD ARE LACKING. TO ADDRESS THIS ISSUE, WE EVALUATED RENAL AND CARDIAC INJURY PROGRESSION AND FUNCTIONAL CHANGES INDUCED BY 4 WK OF DAILY COMBUSTIBLE CIGARETTE SMOKE EXPOSURE IN THE 5/6TH PARTIAL NEPHRECTOMY (PNX) CKD MODEL. MOLECULAR EVALUATIONS REVEALED THAT CIGARETTE SMOKE SIGNIFICANTLY (P < 0.05) DECREASED RENAL AND CARDIAC EXPRESSION OF THE ANTIFIBROTIC MICRORNA MIR-29B-3 AND INCREASED EXPRESSION OF MOLECULAR FIBROSIS MARKERS. IN TERMS OF CARDIAC AND RENAL ORGAN STRUCTURE AND FUNCTION, EXPOSURE TO CIGARETTE SMOKE LED TO SIGNIFICANTLY INCREASED SYSTOLIC BLOOD PRESSURE, CARDIAC HYPERTROPHY, CARDIAC AND RENAL FIBROSIS, AND DECREASED RENAL FUNCTION. THESE DATA INDICATE THAT DECREASED EXPRESSION OF MIR-29B-3P IS A NOVEL MECHANISM WHEREIN CIGARETTE SMOKE PROMOTES ACCELERATED CARDIAC AND RENAL TISSUE INJURY IN CKD. (155 WORDS).	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
11  6569 25 TRANSPLANTATION OF EPIGENETICALLY MODIFIED ADULT CARDIAC C-KIT+ CELLS RETARDS REMODELING AND IMPROVES CARDIAC FUNCTION IN ISCHEMIC HEART FAILURE MODEL. CARDIAC C-KIT+ CELLS HAVE A MODEST CARDIOGENIC POTENTIAL THAT COULD LIMIT THEIR EFFICACY IN HEART DISEASE TREATMENT. THE PRESENT STUDY WAS DESIGNED TO AUGMENT THE CARDIOGENIC POTENTIAL OF CARDIAC C-KIT+ CELLS THROUGH CLASS I HISTONE DEACETYLASE (HDAC) INHIBITION AND EVALUATE THEIR THERAPEUTIC POTENCY IN THE CHRONIC HEART FAILURE (CHF) ANIMAL MODEL. MYOCARDIAL INFARCTION (MI) WAS CREATED BY CORONARY ARTERY OCCLUSION IN RATS. C-KIT+ CELLS WERE TREATED WITH MOCETINOSTAT (MOCE), A SPECIFIC CLASS I HDAC INHIBITOR. AT 3 WEEKS AFTER MI, CHF ANIMALS WERE RETROGRADELY INFUSED WITH UNTREATED (CONTROL) OR MOCE-TREATED C-KIT+ CELLS (MOCE/C-KIT+ CELLS) AND EVALUATED AT 3 WEEKS AFTER CELL INFUSION. WE FOUND THAT CLASS I HDAC INHIBITION IN C-KIT+ CELLS ELEVATED THE LEVEL OF ACETYLATED HISTONE H3 (ACH3) AND INCREASED ACH3 LEVELS IN THE PROMOTER REGIONS OF PLURIPOTENT AND CARDIAC-SPECIFIC GENES. EPIGENETIC CHANGES WERE ACCOMPANIED BY INCREASED EXPRESSION OF CARDIAC-SPECIFIC MARKERS. TRANSPLANTATION OF CHF RATS WITH EITHER CONTROL OR MOCE/C-KIT+ CELLS RESULTED IN AN IMPROVEMENT IN CARDIAC FUNCTION, RETARDATION OF CHF REMODELING MADE EVIDENT BY INCREASED VASCULARIZATION AND SCAR SIZE, AND CARDIOMYOCYTE HYPERTROPHY REDUCTION. COMPARED WITH CHF INFUSED WITH CONTROL CELLS, INFUSION OF MOCE/C-KIT+ CELLS RESULTED IN A FURTHER REDUCTION IN LEFT VENTRICLE END-DIASTOLIC PRESSURE AND TOTAL COLLAGEN AND AN INCREASE IN INTERLEUKIN-6 EXPRESSION. THE LOW ENGRAFTMENT OF INFUSED CELLS SUGGESTS THAT PARACRINE EFFECTS MIGHT ACCOUNT FOR THE BENEFICIAL EFFECTS OF C-KIT+ CELLS IN CHF. IN CONCLUSION, SELECTIVE INHIBITION OF CLASS I HDACS INDUCED EXPRESSION OF CARDIAC MARKERS IN C-KIT+ CELLS AND PARTIALLY AUGMENTED THE EFFICACY OF THESE CELLS FOR CHF REPAIR. SIGNIFICANCE: THE STUDY HAS SHOWN THAT SELECTIVE CLASS 1 HISTONE DEACETYLASE INHIBITION IS SUFFICIENT TO REDIRECT C-KIT+ CELLS TOWARD A CARDIAC FATE. EPIGENETICALLY MODIFIED C-KIT+ CELLS IMPROVED CONTRACTILE FUNCTION AND RETARDED REMODELING OF THE CONGESTIVE HEART FAILURE HEART. THIS STUDY PROVIDES NEW INSIGHTS INTO THE EFFICACY OF CARDIAC C-KIT+ CELLS IN THE ISCHEMIC HEART FAILURE MODEL.	2015	
                                                               
12  5576 35 ROLE OF MICRORNAS IN THE PATHOGENESIS OF DIABETIC CARDIOMYOPATHY. THE MORBIDITY OF DIABETES MELLITUS HAS BEEN INCREASING ANNUALLY. AS A PROGRESSIVE METABOLIC DISORDER, CHRONIC COMPLICATIONS OCCUR IN THE LATE STAGE OF DIABETES. IN ADDITION, CARDIOVASCULAR DISEASES ACCOUNT FOR THE MAJOR CAUSE OF MORBIDITY AND MORTALITY AMONG THE DIABETIC POPULATION WORLDWIDE. DIABETIC CARDIOMYOPATHY (DCM) IS A TYPE OF DIABETIC HEART DISEASE. PATIENTS WITH DCM SHOW SYMPTOMS AND SIGNS OF HEART FAILURE WHILE NO SPECIFIC CAUSE, SUCH AS CORONARY DISEASE, HYPERTENSION, ALCOHOL CONSUMPTION, OR OTHER STRUCTURAL HEART DISEASES HAS BEEN IDENTIFIED. THE PATHOGENESIS OF DCM IS COMPLEX AND HAS NOT BEEN WELL UNDERSTOOD UNTIL RECENTLY. MICRORNAS (MIRS) BELONG TO A NOVEL FAMILY OF HIGHLY CONSERVED, SHORT, NON-CODING, SINGLE-STRANDED RNA MOLECULES THAT REGULATE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL GENE EXPRESSION. FURTHERMORE, RECENT STUDIES HAVE DEMONSTRATED AN ASSOCIATION BETWEEN MIRS AND DCM. IN THE CURRENT REVIEW, THE ROLE OF MIRS IN THE PATHOGENESIS OF DCM IS SUMMARIZED. IT WAS CONCLUDED THAT MIRS CONTRIBUTE TO THE REGULATION OF CARDIOMYOCYTE HYPERTROPHY, MYOCARDIAL FIBROSIS, CARDIOMYOCYTE APOPTOSIS, MITOCHONDRIAL DYSFUNCTION, MYOCARDIAL ELECTRICAL REMODELING, EPIGENETIC MODIFICATION AND VARIOUS OTHER PATHOPHYSIOLOGICAL PROCESSES OF DCM. THESE STUDIES MAY PROVIDE NOVEL INSIGHTS INTO TARGETS FOR PREVENTION AND TREATMENT OF THE DISEASE.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
13   465 35 ARE TARGETED THERAPIES FOR DIABETIC CARDIOMYOPATHY ON THE HORIZON? DIABETES INCREASES THE RISK OF HEART FAILURE APPROXIMATELY 2.5-FOLD, INDEPENDENT OF CORONARY ARTERY DISEASE AND OTHER COMORBIDITIES. THIS PROCESS, TERMED DIABETIC CARDIOMYOPATHY, IS CHARACTERIZED BY INITIAL IMPAIRMENT OF LEFT VENTRICULAR (LV) RELAXATION FOLLOWED BY LV CONTRACTILE DYSFUNCTION. POST-MORTEM EXAMINATION REVEALS THAT HUMAN DIASTOLIC DYSFUNCTION IS CLOSELY ASSOCIATED WITH LV DAMAGE, INCLUDING CARDIOMYOCYTE HYPERTROPHY, APOPTOSIS AND FIBROSIS, WITH IMPAIRED CORONARY MICROVASCULAR PERFUSION. THE PATHOPHYSIOLOGICAL MECHANISMS UNDERPINNING THE CHARACTERISTIC FEATURES OF DIABETIC CARDIOMYOPATHY REMAIN POORLY UNDERSTOOD, ALTHOUGH MULTIPLE FACTORS INCLUDING ALTERED LIPID METABOLISM, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, ENDOPLASMIC RETICULUM (ER) STRESS, INFLAMMATION, AS WELL AS EPIGENETIC CHANGES, ARE IMPLICATED. DESPITE A RECENT RISE IN RESEARCH INTERROGATING THESE MECHANISMS AND AN INCREASED UNDERSTANDING OF THE CLINICAL IMPORTANCE OF DIABETIC CARDIOMYOPATHY, THERE REMAINS A LACK OF SPECIFIC TREATMENT STRATEGIES. HOW THE CHRONIC METABOLIC DISTURBANCES OBSERVED IN DIABETES LEAD TO STRUCTURAL AND FUNCTIONAL CHANGES REMAINS A PERTINENT QUESTION, AND IT IS HOPED THAT RECENT ADVANCES, PARTICULARLY IN THE AREA OF EPIGENETICS, AMONG OTHERS, MAY PROVIDE SOME ANSWERS. THIS REVIEW HENCE EXPLORES THE TEMPORAL ONSET OF THE PATHOLOGICAL FEATURES OF DIABETIC CARDIOMYOPATHY, AND THEIR RELATIVE CONTRIBUTION TO THE RESULTANT DISEASE PHENOTYPE, AS WELL AS BOTH CURRENT AND POTENTIAL THERAPEUTIC OPTIONS. THE EMERGENCE OF GLUCOSE-OPTIMIZING AGENTS, NAMELY GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AGONISTS AND SODIUM/GLUCOSE CO-TRANSPORTER (SGLT)2 INHIBITORS THAT CONFER BENEFITS ON CARDIOVASCULAR OUTCOMES, TOGETHER WITH NOVEL EXPERIMENTAL APPROACHES, HIGHLIGHT A NEW AND EXCITING ERA IN DIABETES RESEARCH, WHICH IS LIKELY TO RESULT IN MAJOR CLINICAL IMPACT.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                  
14  5068 25 PHYSICAL ACTIVITY AND PROGENITOR CELL-MEDIATED ENDOTHELIAL REPAIR IN CHRONIC HEART FAILURE: IS THERE A ROLE FOR EPIGENETICS? CHRONIC HEART FAILURE (CHF) IS THE MOST COMMON CARDIAC DISEASE AMONG THE ELDERLY AND A LEADING CAUSE OF MORTALITY IN ELDERLY PATIENTS. ENDOTHELIAL DYSFUNCTION IS HELD TO HAVE A MAJOR ROLE IN THE DEVELOPMENT AND PROGRESSION OF CHF, WHICH RESULTS IN PROGRESSIVELY IMPAIRED FUNCTIONAL CAPACITY. ENDOTHELIAL PROGENITOR CELLS (EPCS) AND CIRCULATING ANGIOGENIC CELLS (CACS) ARE THE MAIN PLAYERS INVOLVED IN THE ENDOGENOUS REPAIR MECHANISMS THAT CAN COUNTERACT ENDOTHELIAL DYSFUNCTION. A MOUNTING BODY OF DATA INDICATES THAT EXERCISE ENHANCES ENDOTHELIAL RENEWAL THROUGH MOBILIZATION OF BONE MARROW-DERIVED EPCS AND CACS, MAKING IT AN EFFECTIVE THERAPEUTIC TOOL FOR CHF. INTERESTINGLY, EMERGING EVIDENCE HAS BEEN SHOWING THAT EXERCISE TRAINING CAN ALSO PROMOTE EPIGENETIC MODIFICATIONS, E.G. DNA METHYLATION, HISTONE MODIFICATIONS, AND DIFFERENTIAL EXPRESSION OF SPECIFIC NON-CODING RNAS LIKE MICRORNA (MIRNAS). SINCE DEREGULATION OF THE MIRNAS INVOLVED IN ENDOTHELIAL FUNCTION MODULATION HAS WIDELY BEEN DOCUMENTED IN CIRCULATING CELLS AND PLASMA OF CHF PATIENTS, DEREGULATION OF EPIGENETIC FEATURES COULD PLAY A KEY ROLE IN DISEASE PROGRESSION. HERE, WE REVIEW CURRENT KNOWLEDGE OF THE CONTRIBUTION OF EPCS AND CACS TO ENDOTHELIAL REPAIR MECHANISMS IN CHF PATIENTS, FOCUSING ON THE EFFECTS INDUCED BY EXERCISE TRAINING AND HYPOTHESIZING THAT SOME OF THESE EFFECTS CAN BE MEDIATED BY EPIGENETIC MECHANISMS.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
15  2313 30 EPIGENETIC REGULATION OF ENDOTHELIAL CELL FUNCTION BY NUCLEIC ACID METHYLATION IN CARDIAC HOMEOSTASIS AND DISEASE. PATHOLOGICAL REMODELLING OF THE MYOCARDIUM, INCLUDING INFLAMMATION, FIBROSIS AND HYPERTROPHY, IN RESPONSE TO ACUTE OR CHRONIC INJURY IS CENTRAL IN THE DEVELOPMENT AND PROGRESSION OF HEART FAILURE (HF). WHILE BOTH RESIDENT AND INFILTRATING CARDIAC CELLS ARE IMPLICATED IN THESE PATHOPHYSIOLOGICAL PROCESSES, RECENT EVIDENCE HAS SUGGESTED THAT ENDOTHELIAL CELLS (ECS) MAY BE THE PRINCIPAL CELL TYPE RESPONSIBLE FOR ORCHESTRATING PATHOLOGICAL CHANGES IN THE FAILING HEART. EPIGENETIC MODIFICATION OF NUCLEIC ACIDS, INCLUDING DNA, AND MORE RECENTLY RNA, BY METHYLATION IS ESSENTIAL FOR PHYSIOLOGICAL DEVELOPMENT DUE TO THEIR CRITICAL REGULATION OF CELLULAR GENE EXPRESSION. AS ACCUMULATING EVIDENCE HAS HIGHLIGHTED ALTERED PATTERNS OF DNA AND RNA METHYLATION IN HF AT BOTH THE GLOBAL AND INDIVIDUAL GENE LEVELS, MUCH EFFORT HAS BEEN DIRECTED TOWARDS DEFINING THE PRECISE ROLE OF SUCH CELL-SPECIFIC EPIGENETIC CHANGES IN THE CONTEXT OF HF. CONSIDERING THE INCREASINGLY APPARENT CRUCIAL ROLE THAT ECS PLAY IN CARDIAC HOMEOSTASIS AND DISEASE, THIS ARTICLE WILL SPECIFICALLY FOCUS ON NUCLEIC ACID METHYLATION (BOTH DNA AND RNA) IN THE FAILING HEART, EMPHASISING THE KEY INFLUENCE OF THESE EPIGENETIC MECHANISMS IN GOVERNING EC FUNCTION. THIS REVIEW SUMMARISES CURRENT UNDERSTANDING OF DNA AND RNA METHYLATION ALTERATIONS IN HF, ALONG WITH THEIR SPECIFIC ROLE IN REGULATING EC FUNCTION IN RESPONSE TO STRESS (E.G. HYPERGLYCAEMIA, HYPOXIA). IMPROVED APPRECIATION OF THIS IMPORTANT RESEARCH AREA WILL AID IN FURTHER IMPLICATING DYSFUNCTIONAL ECS IN HF PATHOGENESIS, WHILST INFORMING DEVELOPMENT OF EC-TARGETED STRATEGIES AND ADVANCING POTENTIAL TRANSLATION OF EPIGENETIC-BASED THERAPIES FOR SPECIFIC TARGETING OF PATHOLOGICAL CARDIAC REMODELLING IN HF.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
16   543 25 ATRIAL FIBRILLATION IS ASSOCIATED WITH HYPERMETHYLATION IN HUMAN LEFT ATRIUM, AND TREATMENT WITH DECITABINE REDUCES ATRIAL TACHYARRHYTHMIAS IN SPONTANEOUSLY HYPERTENSIVE RATS. ATRIAL FIBRILLATION (AF) IS THE MOST COMMON CARDIAC ARRHYTHMIA. AS THE MOLECULAR MECHANISMS UNDERLYING THE PATHOLOGY ARE LARGELY UNKNOWN, THIS CARDIAC ARRHYTHMIA REMAINS DIFFICULT TO TREAT. TO IDENTIFY SPECIFIC MOLECULAR ACTORS INVOLVED IN AF, WE HAVE PERFORMED A TRANSCRIPTOMIC ANALYSIS ON LEFT ATRIUM (LA) FROM PATIENTS WITH VALVULAR HEART DISEASE WITH OR WITHOUT AF. WE SHOWED THAT 1627 GENES HAD ALTERED BASAL EXPRESSION LEVEL IN LA TISSUE OF AF PATIENTS COMPARED WITH THE CONTROL GROUP. THE SIGNIFICANTLY ENRICHED GENE ONTOLOGY BIOLOGICAL PROCESS "ANATOMICAL STRUCTURE MORPHOGENESIS" CONTAINED THE HIGHEST NUMBER OF GENES IN LINE WITH CHANGES IN STRUCTURE THAT OCCUR WHEN THE HUMAN HEART REMODELS FOLLOWING AF DEVELOPMENT (IE, LA DILATATION AND INTERSTITIAL FIBROSIS). WE THEN FOCUSED THE STUDY ON PITX2 (PAIRED-LIKE HOMEODOMAIN 2), BEING THE MOST ALTERED TRANSCRIPTION FACTOR IN LA FROM AF PATIENTS AND FROM WHICH COMPELLING EVIDENCE HAVE INDICATED THAT ITS REDUCED EXPRESSION CAN BE CONSIDERED AS A MARKER FOR THE DISEASE. IN ADDITION, ITS EXPRESSION WAS INVERSELY CORRELATED WITH LA SIZE. WE DEMONSTRATED THAT AF IS ASSOCIATED WITH PITX2 PROMOTER HYPERMETHYLATION BOTH IN HUMANS AND ARRHYTHMIC AGING SPONTANEOUSLY HYPERTENSIVE RATS. CHRONIC ADMINISTRATION OF A DNA METHYLATION INHIBITOR (IE, 5-AZA-2'-DEOXYCITIDINE) IMPROVED ECG ARRHYTHMIC PROFILES AND SUPEROXIDE DISMUTASE ACTIVITIES AND REDUCED FIBROSIS IN THE LEFT VENTRICLE OF SPONTANEOUSLY HYPERTENSIVE RATS. TAKEN TOGETHER, THESE DATA SUPPORT THE NOTION THAT AF IS ASSOCIATED WITH EPIGENETIC CHANGES IN LA AND PROVIDE A PROOF-OF-CONCEPT THAT HYPOMETHYLATING AGENTS HAVE TO BE CONSIDERED IN THE TREATMENT OF ATRIAL ARRHYTHMIAS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
17   750 19 CARDIAC INVOLVEMENT IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES. AUTHORS HAVE REVIEWED LITERATURE ABOUT THE MANAGEMENT OF PATIENTS WITH CARDIOLOGIC DISEASE OCCURRING SECONDARY TO HEMATOLOGIC PATHOLOGY ITSELF OR ITS THERAPY, WITH A FOCUS ON INFILTRATION OF MYOCARDIUM IN ACUTE AND CHRONIC LEUKEMIA, LYMPHOMA, MULTIPLE MYELOMA, AND HYPEREOSINOPHILIC SYNDROME. MOREOVER, THEY EVALUATED CHEMOTHERAPY-ASSOCIATED TOXICITY, PARTICULARLY FOR NEW DRUGS SUCH AS MONOCLONAL ANTIBODY THERAPY, TYROSINE KINASE INHIBITORS, ARSENIC TRIOXIDE, BORTEZOMIB, AND EPIGENETIC THERAPY. IN FACT, CARDIAC TOXICITY MAY RANGE FROM ASYMPTOMATIC SUBCLINICAL ABNORMALITIES, SUCH AS ELECTROCARDIOGRAPHIC CHANGES AND LEFT VENTRICULAR EJECTION DECLINE, TO LIFE-THREATENING EVENTS AND LEAD TO CHEMOTHERAPY DOSE REDUCTION AND DELAY AND, IN SOME CASES, FOR PATIENTS WITH SEVERE SIDE EFFECTS, DISCONTINUATION OF TREATMENT. FINALLY, THEY DISCUSSED ON THE IDENTIFICATION OF EARLY MARKERS OF CARDIAC INJURY AND ON CARDIAC STEM CELL THERAPY AS A PROMISING APPROACH TO FACILITATE MYOCARDIAL REGENERATION.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
18  4415 29 MOLECULAR AND CELLULAR MECHANISMS THAT INDUCE ARTERIAL CALCIFICATION BY INDOXYL SULFATE AND P-CRESYL SULFATE. THE PROTEIN-BOUND UREMIC TOXINS, INDOXYL SULFATE (IS) AND P-CRESYL SULFATE (PCS), ARE CONSIDERED TO BE HARMFUL VASCULAR TOXINS. ARTERIAL MEDIA CALCIFICATION, OR THE DEPOSITION OF CALCIUM PHOSPHATE CRYSTALS IN THE ARTERIES, CONTRIBUTES SIGNIFICANTLY TO CARDIOVASCULAR COMPLICATIONS, INCLUDING LEFT VENTRICULAR HYPERTROPHY, HYPERTENSION, AND IMPAIRED CORONARY PERFUSION IN THE ELDERLY AND PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD) AND DIABETES. RECENTLY, WE REPORTED THAT BOTH IS AND PCS TRIGGER MODERATE TO SEVERE CALCIFICATION IN THE AORTA AND PERIPHERAL VESSELS OF CKD RATS. THIS REVIEW DESCRIBES THE MOLECULAR AND CELLULAR MECHANISMS BY WHICH THESE UREMIC TOXINS INDUCE ARTERIAL MEDIA CALCIFICATION. A COMPLEX INTERPLAY BETWEEN INFLAMMATION, COAGULATION, AND LIPID METABOLISM PATHWAYS, INFLUENCED BY EPIGENETIC FACTORS, IS CRUCIAL IN IS/PCS-INDUCED ARTERIAL MEDIA CALCIFICATION. HIGH LEVELS OF GLUCOSE ARE LINKED TO THESE EVENTS, SUGGESTING THAT A GOOD BALANCE BETWEEN GLUCOSE AND LIPID LEVELS MIGHT BE IMPORTANT. ON THE CELLULAR LEVEL, EFFECTS ON ENDOTHELIAL CELLS, WHICH ACT AS THE PRIMARY SENSORS OF CIRCULATING PATHOLOGICAL TRIGGERS, MIGHT BE AS IMPORTANT AS THOSE ON VASCULAR SMOOTH MUSCLE CELLS. ENDOTHELIAL DYSFUNCTION, PROVOKED BY IS AND PCS TRIGGERED OXIDATIVE STRESS, MAY BE CONSIDERED A KEY EVENT IN THE ONSET AND DEVELOPMENT OF ARTERIAL MEDIA CALCIFICATION. IN THIS REVIEW A NUMBER OF IMPORTANT OUTSTANDING QUESTIONS SUCH AS THE ROLE OF MIRNA'S, PHENOTYPIC SWITCHING OF BOTH ENDOTHELIAL AND VASCULAR SMOOTH MUSCLE CELLS AND NEW TYPES OF PROGRAMMED CELL DEATH IN ARTERIAL MEDIA CALCIFICATION RELATED TO PROTEIN-BOUND UREMIC TOXINS ARE PUT FORWARD AND DISCUSSED.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19  6374 31 THE ROLE OF MITOCHONDRIA IN MYOCARDIAL DAMAGE CAUSED BY ENERGY METABOLISM DISORDERS: FROM MECHANISMS TO THERAPEUTICS. MYOCARDIAL DAMAGE IS THE MOST SERIOUS PATHOLOGICAL CONSEQUENCE OF CARDIOVASCULAR DISEASES AND AN IMPORTANT REASON FOR THEIR HIGH MORTALITY. IN RECENT YEARS, BECAUSE OF THE HIGH PREVALENCE OF SYSTEMIC ENERGY METABOLISM DISORDERS (E.G., OBESITY, DIABETES MELLITUS, AND METABOLIC SYNDROME), COMPLICATIONS OF MYOCARDIAL DAMAGE CAUSED BY THESE DISORDERS HAVE ATTRACTED WIDESPREAD ATTENTION. ENERGY METABOLISM DISORDERS ARE INDEPENDENT OF TRADITIONAL INJURY-RELATED RISK FACTORS, SUCH AS ISCHEMIA, HYPOXIA, TRAUMA, AND INFECTION. AN IMBALANCE OF MYOCARDIAL METABOLIC FLEXIBILITY AND MYOCARDIAL ENERGY DEPLETION ARE USUALLY THE INITIAL CHANGES OF MYOCARDIAL INJURY CAUSED BY ENERGY METABOLISM DISORDERS, AND ABNORMAL MORPHOLOGY AND FUNCTIONAL DESTRUCTION OF THE MITOCHONDRIA ARE THEIR IMPORTANT FEATURES. SPECIFICALLY, MITOCHONDRIA ARE THE CENTERS OF ENERGY METABOLISM, AND RECENT EVIDENCE HAS SHOWN THAT DECREASED MITOCHONDRIAL FUNCTION, CAUSED BY AN IMBALANCE IN MITOCHONDRIAL QUALITY CONTROL, MAY PLAY A KEY ROLE IN MYOCARDIAL INJURY CAUSED BY ENERGY METABOLISM DISORDERS. UNDER CHRONIC ENERGY STRESS, MITOCHONDRIA UNDERGO PATHOLOGICAL FISSION, WHILE MITOPHAGY, MITOCHONDRIAL FUSION, AND BIOGENESIS ARE INHIBITED, AND MITOCHONDRIAL PROTEIN BALANCE AND TRANSFER ARE DISTURBED, RESULTING IN THE ACCUMULATION OF NONFUNCTIONAL AND DAMAGED MITOCHONDRIA. CONSEQUENTLY, DAMAGED MITOCHONDRIA LEAD TO MYOCARDIAL ENERGY DEPLETION AND THE ACCUMULATION OF LARGE AMOUNTS OF REACTIVE OXYGEN SPECIES, FURTHER AGGRAVATING THE IMBALANCE IN MITOCHONDRIAL QUALITY CONTROL AND FORMING A VICIOUS CYCLE. IN ADDITION, IMPAIRED MITOCHONDRIA COORDINATE CALCIUM HOMEOSTASIS IMBALANCE, AND EPIGENETIC ALTERATIONS PARTICIPATE IN THE PATHOGENESIS OF MYOCARDIAL DAMAGE. THESE PATHOLOGICAL CHANGES INDUCE RAPID PROGRESSION OF MYOCARDIAL DAMAGE, EVENTUALLY LEADING TO HEART FAILURE OR SUDDEN CARDIAC DEATH. TO INTERVENE MORE SPECIFICALLY IN THE MYOCARDIAL DAMAGE CAUSED BY METABOLIC DISORDERS, WE NEED TO UNDERSTAND THE SPECIFIC ROLE OF MITOCHONDRIA IN THIS CONTEXT IN DETAIL. ACCORDINGLY, PROMISING THERAPEUTIC STRATEGIES HAVE BEEN PROPOSED. WE ALSO SUMMARIZE THE EXISTING THERAPEUTIC STRATEGIES TO PROVIDE A REFERENCE FOR CLINICAL TREATMENT AND DEVELOPING NEW THERAPIES.	2023	

20  2486 25 EPIGENETIC-SENSITIVE CHALLENGES OF CARDIOHEPATIC INTERACTIONS: CLINICAL AND THERAPEUTIC IMPLICATIONS IN HEART FAILURE PATIENTS. HEART FAILURE AND LIVER DYSFUNCTION CAN COEXIST OWING TO COMPLEX CARDIOHEPATIC INTERACTIONS INCLUDING THE DEVELOPMENT OF HYPOXIC HEPATITIS AND CONGESTIVE HEPATOPATHY IN PATIENTS WITH HEART FAILURE AS WELL AS 'CIRRHOTIC CARDIOMYOPATHY' IN ADVANCED LIVER DISEASE AND FOLLOWING LIVER TRANSPLANTATION. THE INVOLVEMENT OF LIVER DYSFUNCTION IN PATIENTS WITH HEART FAILURE REFLECTS CRUCIAL SYSTEMIC HEMODYNAMIC MODIFICATIONS OCCURRING DURING THE EVOLUTION OF THIS SYNDROME. THE ARTERIAL HYPOPERFUSION AND DOWNSTREAM HYPOXIA CAN LEAD TO HYPOXIC HEPATITIS IN ACUTE HEART FAILURE PATIENTS WHEREAS PASSIVE CONGESTION IS CORRELATED WITH CONGESTIVE HEPATOPATHY OCCURRING IN PATIENTS WITH CHRONIC HEART FAILURE. NOWADAYS, LIQUID BIOPSY STRATEGIES MEASURING LIVER FUNCTION ARE WELL ESTABLISHED IN EVALUATING THE PROGNOSIS OF PATIENTS WITH HEART FAILURE. LARGE RANDOMIZED CLINICAL TRIALS CONFIRMED THAT GAMMA-GLUTAMYLTRANSFERASE, BILIRUBIN, LACTATE DEIHYDROGENASE, AND TRANSAMINASES ARE USEFUL PROGNOSTIC BIOMARKERS IN PATIENTS WITH HEART FAILURE AFTER TRANSPLANTATION. DEEPER KNOWLEDGE ABOUT THE PATHOGENIC MECHANISMS UNDERLYING CARDIOHEPATIC INTERACTIONS WOULD BE USEFUL TO IMPROVE DIAGNOSIS, PROGNOSIS, AND TREATMENTS OF THESE COMORBID PATIENTS. EPIGENETIC-SENSITIVE MODIFICATIONS ARE HERITABLE CHANGES TO GENE EXPRESSION WITHOUT INVOLVING DNA SEQUENCE, COMPRISING DNA METHYLATION, HISTONE MODIFICATIONS, AND NONCODING RNAS WHICH SEEM TO BE RELEVANT IN THE PATHOGENESIS OF HEART FAILURE AND LIVER DISEASES WHEN CONSIDERED IN A SEPARATE WAY. THE GOAL OF OUR REVIEW IS TO HIGHLIGHT THE PERTINENCE OF DETECTING EPIGENETIC MODIFICATIONS DURING THE COMPLEX CARDIOHEPATIC INTERACTIONS IN CLINICAL SETTING. MOREOVER, WE PROPOSE A CLINICAL RESEARCH PROGRAM WHICH MAY BE USEFUL TO IDENTIFY EPIGENETIC-SENSITIVE BIOMARKERS OF CARDIOHEPATIC INTERACTIONS AND ADVANCE PERSONALIZED THERAPY IN THESE COMORBID PATIENTS.	2021