1 5596 104 ROLES OF HISTONE ACETYLATION MODIFIERS AND OTHER EPIGENETIC REGULATORS IN VASCULAR CALCIFICATION. VASCULAR CALCIFICATION (VC) IS CHARACTERIZED BY CALCIUM DEPOSITION INSIDE ARTERIES AND IS CLOSELY ASSOCIATED WITH THE MORBIDITY AND MORTALITY OF ATHEROSCLEROSIS, CHRONIC KIDNEY DISEASE, DIABETES, AND OTHER CARDIOVASCULAR DISEASES (CVDS). VC IS NOW WIDELY KNOWN TO BE AN ACTIVE PROCESS OCCURRING IN VASCULAR SMOOTH MUSCLE CELLS (VSMCS) INVOLVING MULTIPLE MECHANISMS AND FACTORS. THESE MECHANISMS SHARE FEATURES WITH THE PROCESS OF BONE FORMATION, SINCE THE PHENOTYPE SWITCHING FROM THE CONTRACTILE TO THE OSTEOCHONDROGENIC PHENOTYPE ALSO OCCURS IN VSMCS DURING VC. IN ADDITION, VC CAN BE REGULATED BY EPIGENETIC FACTORS, INCLUDING DNA METHYLATION, HISTONE MODIFICATION, AND NONCODING RNAS. ALTHOUGH VC IS COMMONLY OBSERVED IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND CVD, SPECIFIC DRUGS FOR VC HAVE NOT BEEN DEVELOPED. THUS, DISCOVERING NOVEL THERAPEUTIC TARGETS MAY BE NECESSARY. IN THIS REVIEW, WE SUMMARIZE THE CURRENT EXPERIMENTAL EVIDENCE REGARDING THE ROLE OF EPIGENETIC REGULATORS INCLUDING HISTONE DEACETYLASES AND PROPOSE THE THERAPEUTIC IMPLICATION OF THESE REGULATORS IN THE TREATMENT OF VC. 2020 2 6699 48 VASCULAR CALCIFICATION IN CKD: NEW INSIGHTS INTO ITS MECHANISMS. VASCULAR CALCIFICATION (VC) IS A COMMON COMPLICATION OF CHRONIC KIDNEY DISEASE (CKD) AND CONTRIBUTES TO AN INCREASED RISK OF CARDIOVASCULAR MORBIDITY AND MORTALITY. HOWEVER, EFFECTIVE THERAPIES ARE STILL UNAVAILABLE AT PRESENT. IT HAS BEEN WELL ESTABLISHED THAT VC ASSOCIATED WITH CKD IS NOT A PASSIVE PROCESS OF CALCIUM PHOSPHATE DEPOSITION, BUT AN ACTIVELY REGULATED AND CELL-MEDIATED PROCESS THAT SHARES MANY SIMILARITIES WITH BONE FORMATION. ADDITIONALLY, NUMEROUS STUDIES HAVE SUGGESTED THAT CKD PATIENTS HAVE SPECIFIC RISK FACTORS AND CONTRIBUTORS TO THE DEVELOPMENT OF VC, SUCH AS HYPERPHOSPHATEMIA, UREMIC TOXINS, OXIDATIVE STRESS AND INFLAMMATION. ALTHOUGH RESEARCH EFFORTS IN THE PAST DECADE HAVE GREATLY IMPROVED OUR KNOWLEDGE OF THE MULTIPLE FACTORS AND MECHANISMS INVOLVED IN CKD-RELATED VC, MANY QUESTIONS REMAIN UNANSWERED. MOREOVER, STUDIES FROM THE PAST DECADE HAVE DEMONSTRATED THAT EPIGENETIC MODIFICATIONS ABNORMALITIES, SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS AND NONCODING RNAS, PLAY AN IMPORTANT ROLE IN THE REGULATION OF VC. THIS REVIEW SEEKS TO PROVIDE AN OVERVIEW OF THE PATHOPHYSIOLOGICAL AND MOLECULAR MECHANISMS OF VC ASSOCIATED WITH CKD, MAINLY FOCUSING ON THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS IN THE INITIATION AND PROGRESSION OF UREMIC VC, WITH THE AIM TO DEVELOP PROMISING THERAPIES FOR CKD-RELATED CARDIOVASCULAR EVENTS IN THE FUTURE. 2023 3 3366 33 HISTONE METHYLATION RELATED THERAPEUTIC CHALLENGE IN CARDIOVASCULAR DISEASES. THE EPIDEMIC OF CARDIOVASCULAR DISEASES (CVDS) IS PREDICTED TO SPREAD RAPIDLY IN ADVANCED COUNTRIES ACCOMPANIED BY THE HIGH PREVALENCE OF RISK FACTORS. IN TERMS OF PATHOGENESIS, THE PATHOPHYSIOLOGY OF CVDS IS FEATURED BY MULTIPLE DISORDERS, INCLUDING VASCULAR INFLAMMATION ACCOMPANIED BY SIMULTANEOUSLY PERTURBED PATHWAYS, SUCH AS CELL DEATH AND ACUTE/CHRONIC INFLAMMATORY REACTIONS. EPIGENETIC ALTERATION IS INVOLVED IN THE REGULATION OF GENOME STABILIZATION AND CELLULAR HOMEOSTASIS. THE ASSOCIATION BETWEEN CVD PROGRESSION AND HISTONE MODIFICATIONS IS WIDELY KNOWN. AMONG THE HISTONE MODIFICATIONS, HISTONE METHYLATION IS A REVERSIBLE PROCESS INVOLVED IN THE DEVELOPMENT AND HOMEOSTASIS OF THE CARDIOVASCULAR SYSTEM. ABNORMAL METHYLATION CAN PROMOTE CVD PROGRESSION. THIS REVIEW DISCUSSES HISTONE METHYLATION AND THE ENZYMES INVOLVED IN THE CARDIOVASCULAR SYSTEM AND DETERMINE THE EFFECTS OF HISTONE METHYLTRANSFERASES AND DEMETHYLASES ON THE PATHOGENESIS OF CVDS. WE WILL FURTHER DEMONSTRATE KEY PROTEINS MEDIATED BY HISTONE METHYLATION IN BLOOD VESSELS AND REVIEW HISTONE METHYLATION-MEDIATED CARDIOMYOCYTES AND CELLULAR FUNCTIONS AND PATHWAYS IN CVDS. FINALLY, WE WILL SUMMARIZE THE ROLE OF INHIBITORS OF HISTONE METHYLATION AND DEMETHYLATION IN CVDS AND ANALYZE THEIR THERAPEUTIC POTENTIAL, BASED ON PREVIOUS STUDIES. 2021 4 6700 44 VASCULAR CALCIFICATION MECHANISMS: UPDATES AND RENEWED INSIGHT INTO SIGNALING PATHWAYS INVOLVED IN HIGH PHOSPHATE-MEDIATED VASCULAR SMOOTH MUSCLE CELL CALCIFICATION. VASCULAR CALCIFICATION (VC) IS ASSOCIATED WITH AGING, CARDIOVASCULAR AND RENAL DISEASES AND RESULTS IN POOR MORBIDITY AND INCREASED MORTALITY. VC OCCURS IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD), A CONDITION THAT IS ASSOCIATED WITH HIGH SERUM PHOSPHATE (PI) AND SEVERE CARDIOVASCULAR CONSEQUENCES. HIGH SERUM PI LEVEL IS RELATED TO SOME PATHOLOGIES WHICH AFFECT THE BEHAVIOUR OF VASCULAR CELLS, INCLUDING PLATELETS, ENDOTHELIAL CELLS (ECS) AND SMOOTH MUSCLE CELLS (SMCS), AND PLAYS A CENTRAL ROLE IN PROMOTING VC. VC IS A COMPLEX, ACTIVE AND CELL-MEDIATED PROCESS INVOLVING THE TRANSDIFFERENTIATION OF VASCULAR SMCS TO A BONE-LIKE PHENOTYPE, SYSTEMIC INFLAMMATION, DECREASED ANTI-CALCIFIC EVENTS (LOSS OF CALCIFICATION INHIBITORS), LOSS IN SMC LINEAGE MARKERS AND ENHANCED PRO-CALCIFIC MICRORNAS (MIRS), AN INCREASED INTRACELLULAR CALCIUM LEVEL, APOPTOSIS, ABERRANT DNA DAMAGE RESPONSE (DDR) AND SENESCENCE OF VASCULAR SMCS. THIS REVIEW GIVES A BRIEF OVERVIEW OF THE CURRENT KNOWLEDGE OF VC MECHANISMS WITH A PARTICULAR FOCUS ON PI-INDUCED CHANGES IN THE VASCULAR WALL IMPORTANT IN PROMOTING CALCIFICATION. IN ADDITION TO REVIEWING THE MAIN FINDINGS, THIS REVIEW ALSO SHEDS LIGHT ON DIRECTIONS FOR FUTURE RESEARCH IN THIS AREA AND DISCUSSES EMERGING PATHWAYS SUCH AS PI-REGULATED INTRACELLULAR CALCIUM SIGNALING, EPIGENETICS, OXIDATIVE DNA DAMAGE AND SENESCENCE-MEDIATED MECHANISMS THAT MAY PLAY CRITICAL, YET TO BE EXPLORED, REGULATORY AND DRUGGABLE ROLES IN LIMITING VC. 2021 5 3344 28 HISTONE DEACETYLASES (HDACS) AND ATHEROSCLEROSIS: A MECHANISTIC AND PHARMACOLOGICAL REVIEW. ATHEROSCLEROSIS (AS), THE MOST COMMON UNDERLYING PATHOLOGY FOR CORONARY ARTERY DISEASE, IS A CHRONIC INFLAMMATORY, PROLIFERATIVE DISEASE IN LARGE- AND MEDIUM-SIZED ARTERIES. THE VASCULAR ENDOTHELIUM IS IMPORTANT FOR MAINTAINING VASCULAR HEALTH. ENDOTHELIAL DYSFUNCTION IS A CRITICAL EARLY EVENT LEADING TO AS, WHICH IS A MAJOR RISK FACTOR FOR STROKE AND MYOCARDIAL INFARCTION. ACCUMULATING EVIDENCE HAS SUGGESTED THE CRITICAL ROLES OF HISTONE DEACETYLASES (HDACS) IN REGULATING VASCULAR CELL HOMEOSTASIS AND AS. THE PURPOSE OF THIS REVIEW IS TO PRESENT AN UPDATED VIEW ON THE ROLES OF HDACS (CLASS I, CLASS II, CLASS IV) AND HDAC INHIBITORS IN VASCULAR DYSFUNCTION AND AS. WE ALSO ELABORATE ON THE NOVEL THERAPEUTIC TARGETS AND AGENTS IN ATHEROSCLEROTIC CARDIOVASCULAR DISEASES. 2020 6 4668 35 NEW INSIGHTS INTO MOLECULAR MECHANISMS OF EPIGENETIC REGULATION IN KIDNEY DISEASE. THE NUMBER OF PATIENTS WITH KIDNEY FAILURE HAS INCREASED IN RECENT YEARS. DIFFERENT FACTORS CONTRIBUTE TO THE PROGRESSION OF CHRONIC KIDNEY DISEASE, INCLUDING GLOMERULAR SCLEROSIS, ATHEROSCLEROSIS OF THE RENAL ARTERIES AND TUBULOINTERSTITIAL FIBROSIS. TUBULOINTERSTITIAL INJURY IS INDUCED BY HYPOXIA AND OTHER INFLAMMATORY SIGNALS, LEADING TO FIBROBLAST ACTIVATION. TECHNOLOGICAL ADVANCES USING HIGH-THROUGHPUT SEQUENCING HAS ENABLED THE DETERMINATION OF THE EXPRESSION PROFILE OF ALMOST ALL GENES, REVEALING THAT GENE EXPRESSION IS INTRICATELY REGULATED BY DNA METHYLATION, HISTONE MODIFICATION, CHANGES IN CHROMOSOME CONFORMATION, LONG NON-CODING RNAS AND MICRORNAS. THESE EPIGENETIC MODIFICATIONS ARE STORED AS CELLULAR EPIGENETIC MEMORY. EPIGENETIC MEMORY LEADS TO ADULT-ONSET DISEASE OR AGEING IN THE LONG TERM AND MAY POSSIBLY PLAY AN IMPORTANT ROLE IN THE KIDNEY DISEASE PROCESS. HEREIN WE EMPHASIZE THE IMPORTANCE OF CLARIFYING THE MOLECULAR MECHANISMS UNDERLYING EPIGENETIC MODIFICATIONS BECAUSE THIS MAY LEAD TO THE DEVELOPMENT OF NEW THERAPEUTIC TARGETS IN KIDNEY DISEASE. 2016 7 2532 32 EPIGENETICS IN ATHEROSCLEROSIS AND INFLAMMATION. ATHEROSCLEROSIS IS A MULTIFACTORIAL DISEASE WITH A SEVERE BURDEN ON WESTERN SOCIETY. RECENT INSIGHTS INTO THE PATHOGENESIS OF ATHEROSCLEROSIS UNDERSCORE THE IMPORTANCE OF CHRONIC INFLAMMATION IN BOTH THE INITIATION AND PROGRESSION OF VASCULAR REMODELLING. EXPRESSION OF IMMUNOREGULATORY MOLECULES BY VASCULAR WALL COMPONENTS WITHIN THE ATHEROSCLEROTIC LESIONS IS ACCORDINGLY THOUGHT TO CONTRIBUTE TO THE ONGOING INFLAMMATORY PROCESS. BESIDES GENE REGULATORY PROTEINS (TRANSCRIPTION FACTORS), EPIGENETIC MECHANISMS ALSO PLAY AN ESSENTIAL AND FUNDAMENTAL ROLE IN THE TRANSCRIPTIONAL CONTROL OF GENE EXPRESSION. THESE EPIGENETIC MECHANISMS CHANGE THE ACCESSIBILITY OF CHROMATIN BY DNA METHYLATION AND HISTONE MODIFICATIONS. EPIGENETIC MODULATORS ARE THUS CRITICALLY INVOLVED IN THE REGULATION OF VASCULAR, IMMUNE AND TISSUE-SPECIFIC GENE EXPRESSION WITHIN THE ATHEROSCLEROTIC LESION. IMPORTANTLY, EPIGENETIC PROCESSES ARE REVERSIBLE AND MAY PROVIDE AN EXCELLENT THERAPEUTIC TARGET. THE CONCEPT OF EPIGENETIC REGULATION IS GRADUALLY BEING RECOGNIZED AS AN IMPORTANT FACTOR IN THE PATHOGENESIS OF ATHEROSCLEROSIS. RECENT RESEARCH PROVIDES AN ESSENTIAL LINK BETWEEN INFLAMMATION AND REPROGRAMMING OF THE EPIGENOME. IN THIS REVIEW WE THEREFORE DISCUSS THE BASIS OF EPIGENETIC REGULATION - AND THE CONTRIBUTION THEREOF IN THE REGULATION OF INFLAMMATORY PROCESSES IN GENERAL AND DURING ATHEROSCLEROSIS IN PARTICULAR. MOREOVER WE HIGHLIGHT POTENTIAL THERAPEUTIC INTERVENTIONS BASED ON EPIGENETIC MECHANISMS. 2010 8 607 32 BEYOND GENETICS: EPIGENETIC CODE IN CHRONIC KIDNEY DISEASE. EPIGENETICS REFERS TO A HERITABLE CHANGE IN THE PATTERN OF GENE EXPRESSION THAT IS MEDIATED BY A MECHANISM SPECIFICALLY NOT DUE TO ALTERATIONS IN THE PRIMARY NUCLEOTIDE SEQUENCE. WELL-KNOWN EPIGENETIC MECHANISMS ENCOMPASS DNA METHYLATION, CHROMATIN REMODELING (HISTONE MODIFICATIONS), AND RNA INTERFERENCE. FUNCTIONALLY, EPIGENETICS PROVIDES AN EXTRA LAYER OF TRANSCRIPTIONAL CONTROL AND PLAYS A CRUCIAL ROLE IN NORMAL PHYSIOLOGICAL DEVELOPMENT, AS WELL AS IN PATHOLOGICAL CONDITIONS. ABERRANT DNA METHYLATION IS IMPLICATED IN IMMUNE DYSFUNCTION, INFLAMMATION, AND INSULIN RESISTANCE. EPIGENETIC CHANGES MAY BE RESPONSIBLE FOR 'METABOLIC MEMORY' AND DEVELOPMENT OF MICRO- AND MACROVASCULAR COMPLICATIONS OF DIABETES. MICRORNAS ARE CRITICAL IN THE MAINTENANCE OF GLOMERULAR HOMEOSTASIS AND HENCE RNA INTERFERENCE MAY BE IMPORTANT IN THE PROGRESSION OF RENAL DISEASE. RECENT STUDIES HAVE SHOWN THAT EPIGENETIC MODIFICATIONS ORCHESTRATE THE EPITHELIAL-MESENCHYMAL TRANSITION AND EVENTUALLY FIBROSIS OF THE RENAL TISSUE. OXIDATIVE STRESS, INFLAMMATION, HYPERHOMOCYSTEINEMIA, AND UREMIC TOXINS COULD INDUCE EPIMUTATIONS IN CHRONIC KIDNEY DISEASE. EPIGENETIC ALTERATIONS ARE ASSOCIATED WITH INFLAMMATION AND CARDIOVASCULAR DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE. REVERSIBLE NATURE OF THE EPIGENETIC CHANGES GIVES A UNIQUE OPPORTUNITY TO HALT OR EVEN REVERSE THE DISEASE PROCESS THROUGH TARGETED THERAPEUTIC STRATEGIES. 2011 9 6219 28 THE KEY ROLE OF DNA METHYLATION AND HISTONE ACETYLATION IN EPIGENETICS OF ATHEROSCLEROSIS. ATHEROSCLEROSIS, WHICH IS THE MOST COMMON CHRONIC DISEASE OF THE CORONARY ARTERY, CONSTITUTES A VASCULAR PATHOLOGY INDUCED BY INFLAMMATION AND PLAQUE ACCUMULATION WITHIN ARTERIAL VESSEL WALLS. BOTH DNA METHYLATION AND HISTONE MODIFICATIONS ARE EPIGENETIC CHANGES RELEVANT FOR ATHEROSCLEROSIS. RECENT STUDIES HAVE SHOWN THAT THE DNA METHYLATION AND HISTONE MODIFICATION SYSTEMS ARE CLOSELY INTERRELATED AND MECHANICALLY DEPENDENT ON EACH OTHER. HEREIN, WE EXPLORE THE FUNCTIONAL LINKAGE BETWEEN THESE SYSTEMS, WITH A PARTICULAR EMPHASIS ON SEVERAL RECENT FINDINGS SUGGESTING THAT HISTONE ACETYLATION CAN HELP IN TARGETING DNA METHYLATION AND THAT DNA METHYLATION MAY CONTROL GENE EXPRESSION DURING ATHEROSCLEROSIS. 2020 10 2195 31 EPIGENETIC MODIFICATION MECHANISMS INVOLVED IN INFLAMMATION AND FIBROSIS IN RENAL PATHOLOGY. THE GROWING INCIDENCE OF OBESITY, HYPERTENSION, AND DIABETES, COUPLED WITH THE AGING OF THE POPULATION, IS INCREASING THE PREVALENCE OF RENAL DISEASES IN OUR SOCIETY. CHRONIC KIDNEY DISEASE (CKD) IS CHARACTERIZED BY PERSISTENT INFLAMMATION, FIBROSIS, AND LOSS OF RENAL FUNCTION LEADING TO END-STAGE RENAL DISEASE. NOWADAYS, CKD TREATMENT HAS LIMITED EFFECTIVENESS UNDERSCORING THE IMPORTANCE OF THE DEVELOPMENT OF INNOVATIVE THERAPEUTIC OPTIONS. RECENT STUDIES HAVE IDENTIFIED HOW EPIGENETIC MODIFICATIONS PARTICIPATE IN THE SUSCEPTIBILITY TO CKD AND HAVE EXPLAINED HOW THE ENVIRONMENT INTERACTS WITH THE RENAL CELL EPIGENOME TO CONTRIBUTE TO RENAL DAMAGE. EPIGENETIC MECHANISMS REGULATE CRITICAL PROCESSES INVOLVED IN GENE REGULATION AND DOWNSTREAM CELLULAR RESPONSES. THE MOST RELEVANT EPIGENETIC MODIFICATIONS THAT PLAY A CRITICAL ROLE IN RENAL DAMAGE INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, AND CHANGES IN MIRNA LEVELS. IMPORTANTLY, THESE EPIGENETIC MODIFICATIONS ARE REVERSIBLE AND, THEREFORE, A SOURCE OF POTENTIAL THERAPEUTIC TARGETS. HERE, WE WILL EXPLAIN HOW EPIGENETIC MECHANISMS MAY REGULATE ESSENTIAL PROCESSES INVOLVED IN RENAL PATHOLOGY AND HIGHLIGHT SOME POSSIBLE EPIGENETIC THERAPEUTIC STRATEGIES FOR CKD TREATMENT. 2018 11 2168 31 EPIGENETIC MECHANISMS IN MONOCYTES/MACROPHAGES REGULATE INFLAMMATION IN CARDIOMETABOLIC AND VASCULAR DISEASE. CARDIOMETABOLIC AND VASCULAR DISEASE, WITH THEIR ASSOCIATED SECONDARY COMPLICATIONS, ARE THE LEADING CAUSE OF MORBIDITY AND MORTALITY IN WESTERN SOCIETY. CHRONIC INFLAMMATION IS A COMMON THEME THAT UNDERLIES INITIATION AND PROGRESSION OF CARDIOVASCULAR DISEASE. IN THIS REGARD, MONOCYTES/MACROPHAGES ARE KEY PLAYERS IN THE DEVELOPMENT OF A CHRONIC INFLAMMATORY STATE. OVER THE PAST DECADE, EPIGENETIC MODIFICATIONS, SUCH AS DNA METHYLATION AND POSTTRANSLATIONAL HISTONE PROCESSING, HAVE EMERGED AS IMPORTANT REGULATORS OF IMMUNE CELL PHENOTYPES. ACCUMULATING STUDIES REVEAL THE IMPORTANCE OF EPIGENETIC ENZYMES IN THE DYNAMIC REGULATION OF KEY SIGNALING PATHWAYS THAT ALTER MONOCYTE/MACROPHAGE PHENOTYPES IN RESPONSE TO ENVIRONMENTAL STIMULI. IN THIS REVIEW, WE HIGHLIGHT THE CURRENT PARADIGMS OF MONOCYTE/MACROPHAGE POLARIZATION AND THE EMERGING ROLE OF EPIGENETIC MODIFICATION IN THE REGULATION OF MONOCYTE/MACROPHAGE PHENOTYPE IN OBESITY, DIABETES MELLITUS, ATHEROSCLEROSIS, AND ABDOMINAL AORTIC ANEURYSMS. 2019 12 4467 36 MOLECULAR MECHANISMS OF VASCULAR HEALTH: INSIGHTS FROM VASCULAR AGING AND CALCIFICATION. CARDIOVASCULAR DISEASE IS THE MOST COMMON CAUSE OF DEATH WORLDWIDE, ESPECIALLY BEYOND THE AGE OF 65 YEARS, WITH THE VAST MAJORITY OF MORBIDITY AND MORTALITY DUE TO MYOCARDIAL INFARCTION AND STROKE. VASCULAR PATHOLOGY STEMS FROM A COMBINATION OF GENETIC RISK, ENVIRONMENTAL FACTORS, AND THE BIOLOGIC CHANGES ASSOCIATED WITH AGING. THE PATHOGENESIS UNDERLYING THE DEVELOPMENT OF VASCULAR AGING, AND VASCULAR CALCIFICATION WITH AGING, IN PARTICULAR, IS STILL NOT FULLY UNDERSTOOD. ACCUMULATING DATA SUGGESTS THAT GENETIC RISK, LIKELY COMPOUNDED BY EPIGENETIC MODIFICATIONS, ENVIRONMENTAL FACTORS, INCLUDING DIABETES AND CHRONIC KIDNEY DISEASE, AND THE PLASTICITY OF VASCULAR SMOOTH MUSCLE CELLS TO ACQUIRE AN OSTEOGENIC PHENOTYPE ARE MAJOR DETERMINANTS OF AGE-ASSOCIATED VASCULAR CALCIFICATION. UNDERSTANDING THE MOLECULAR MECHANISMS UNDERLYING GENETIC AND MODIFIABLE RISK FACTORS IN REGULATING AGE-ASSOCIATED VASCULAR PATHOLOGY MAY INSPIRE STRATEGIES TO PROMOTE HEALTHY VASCULAR AGING. THIS ARTICLE SUMMARIZES CURRENT KNOWLEDGE OF CONCEPTS AND MECHANISMS OF AGE-ASSOCIATED VASCULAR DISEASE, WITH AN EMPHASIS ON VASCULAR CALCIFICATION. 2023 13 3772 29 INTERACTION BETWEEN MICRORNA AND DNA METHYLATION IN ATHEROSCLEROSIS. ATHEROSCLEROSIS (AS) IS A CHRONIC INFLAMMATORY DISEASE ACCOMPANIED BY COMPLEX PATHOLOGICAL CHANGES, SUCH AS ENDOTHELIAL DYSFUNCTION, FOAM CELL FORMATION, AND VASCULAR SMOOTH MUSCLE CELL PROLIFERATION. MANY APPROACHES, INCLUDING REGULATING AS-RELATED GENE EXPRESSION IN THE TRANSCRIPTIONAL OR POST-TRANSCRIPTIONAL LEVEL, CONTRIBUTE TO ALLEVIATING AS DEVELOPMENT. THE DNA METHYLATION IS A CRUCIAL EPIGENETIC MODIFICATION IN REGULATING CELL FUNCTION BY SILENCING THE RELATIVE GENE EXPRESSION. THE MICRORNA (MIRNA) IS A TYPE OF NONCODING RNA THAT PLAYS AN IMPORTANT ROLE IN GENE POST-TRANSCRIPTIONAL REGULATION AND DISEASE DEVELOPMENT. THE DNA METHYLATION AND THE MIRNA ARE IMPORTANT EPIGENETIC FACTORS IN AS. HOWEVER, RECENT STUDIES HAVE FOUND A MUTUAL REGULATION BETWEEN THESE TWO FACTORS IN AS DEVELOPMENT. IN THIS STUDY, RECENT INSIGHTS INTO THE ROLES OF MIRNA AND DNA METHYLATION AND THEIR INTERACTION IN THE AS PROGRESSION ARE REVIEWED. 2021 14 2490 33 EPIGENETICALLY REGULATED INFLAMMATION IN VASCULAR SENESCENCE AND RENAL PROGRESSION OF CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) AND ITS COMPLICATIONS, INCLUDING VASCULAR SENESCENCE AND PROGRESSIVE RENAL FIBROSIS, ARE ASSOCIATED WITH INFLAMMATION. VASCULAR SENESCENCE, IN PARTICULAR, HAS EMERGED AS AN INSTRUMENTAL MEDIATOR OF VASCULAR INFLAMMATION THAT POTENTIALLY WORSENS RENAL FUNCTION. EPIGENETICALLY REGULATED INFLAMMATION INVOLVING HISTONE MODIFICATION, DNA METHYLATION, ACTIONS OF MICRORNAS AND OTHER NON-CODING RNAS, AND THEIR RECIPROCAL REACTIONS DURING VASCULAR SENESCENCE AND INFLAMMAGING ARE UNDERAPPRECIATED. THEIR SYNERGISTIC EFFECTS CAN CONTRIBUTE TO CKD PROGRESSION. VASCULAR SENOTHERAPEUTICS OR PHARMACOLOGICAL ANTI-SENESCENT THERAPIES BASED ON EPIGENETIC MACHINERIES CAN THEREFORE BE PLAUSIBLE OPTIONS FOR AMELIORATING VASCULAR AGING AND EVEN HALTING THE WORSENING OF RENAL FIBROSIS. THESE INCLUDE HISTONE DEACETYLASE MODULATORS, HISTONE METHYLTRANSFERASE MODULATORS, OTHER HISTONE MODIFICATION EFFECTORS, DNA METHYLTRANSFERASE INHIBITORS, TELOMERASE REVERSE TRANSCRIPTASE ENHANCERS, MICRORNA MIMIC DELIVERY, AND SMALL MOLECULES WITH MICRORNA-REGULATING POTENTIALS. SOME OF THESE MOLECULES HAVE ALREADY BEEN TESTED AND HAVE SHOWN ANECDOTAL EVIDENCE FOR TREATING UREMIC VASCULOPATHY AND RENAL FIBROSIS, SUPPORTING THE FEASIBILITY OF THIS APPROACH. 2022 15 538 28 ATHEROSCLEROSIS AND EPIGENETIC MODIFICATIONS IN CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS ONE OF THE MOST COMMON CHRONIC DISEASES WORLDWIDE, WITH PREVALENCE CURRENTLY PROJECTED AT 10% AND RISING. CARDIOVASCULAR DISEASE IS THE LEADING CAUSE OF MORBIDITY AND MORTALITY IN CKD PATIENTS AND IS INTEGRALLY LINKED WITH ATHEROGENESIS AND VASCULAR STIFFNESS. ESTIMATED GLOMERULAR FILTRATION RATE AND THE LEVEL OF PROTEINURIA ARE NOT ONLY MARKERS OF KIDNEY FUNCTION BUT OF CARDIOVASCULAR RISK, AS WELL. DESPITE THE EFFORTS, CKD PATIENTS STILL EXPERIENCE EXCESSIVE CARDIOVASCULAR BURDEN. MICRORNAS (MIRNAS) ARE SMALL (18-24 NUCLEOTIDES), SINGLE-STRANDED NON-CODING RNAS THAT REGULATE GENE EXPRESSION BY BLOCKING MESSENGER RNA (MRNA) TRANSLATION AND INITIATING DEGRADATION OF MRNA. STUDIES HAVE CONFIRMED THE IMPERATIVE ROLE OF MIRNA DYSREGULATION IN THE PATHOPHYSIOLOGY OF SEVERAL DISEASES, INCLUDING ATHEROSCLEROSIS AND CKD. THIS ARTICLE SUMMARIZES WHAT IS CURRENTLY KNOWN ABOUT THE ROLE OF MIRNAS IN CKD PATIENTS. 2023 16 3326 35 HISTONE DEACETYLASE 3 (HDAC3) AS AN IMPORTANT EPIGENETIC REGULATOR OF KIDNEY DISEASES. DEVELOPMENT AND PROGRESSION OF MANY KIDNEY DISEASES ARE SUBSTANTIALLY INFLUENCED BY ABERRANT PROTEIN ACETYLATION MODIFICATIONS OF GENE EXPRESSION CRUCIAL FOR KIDNEY FUNCTIONS. HISTONE DEACETYLASE (HDAC) EXPRESSION ALTERATIONS ARE DETECTED FROM RENAL SAMPLES OF PATIENTS AND ANIMAL MODELS OF VARIOUS KIDNEY DISEASES, AND THE ADMINISTRATIONS OF HDAC INHIBITORS DISPLAY IMPRESSIVE RENAL PROTECTIVE EFFECTS IN VITRO AND IN VIVO. HOWEVER, WHEN THE EXPRESSION ALTERATIONS OF MULTIPLE HDACS OCCUR, NOT ALL THE HDACS CAUSALLY AFFECT THE DISEASE ONSET OR PROGRESSION. IDENTIFICATION OF A SINGLE HDAC AS A DISEASE-CAUSING FACTOR WILL ALLOW SUBTYPE-TARGETED INTERVENTION WITH LESS SIDE EFFECT. HDAC3 IS A UNIQUE HDAC WITH DISTINCT STRUCTURAL AND SUBCELLULAR DISTRIBUTION FEATURES AND CO-REPRESSOR DEPENDENCY. HDAC3 IS REQUIRED FOR KIDNEY DEVELOPMENT AND ITS ABERRATIONS ACTIVELY PARTICIPATE IN MANY PATHOLOGICAL PROCESSES, SUCH AS CANCER, CARDIOVASCULAR DISEASES, DIABETES, AND NEURODEGENERATIVE DISORDERS, AND CONTRIBUTE SIGNIFICANTLY TO THE PATHOGENESIS OF KIDNEY DISEASES. THIS REVIEW WILL DISCUSS THE RECENT STUDIES THAT INVESTIGATE THE CRITICAL ROLES OF HDAC3 ABERRATIONS IN KIDNEY DEVELOPMENT, RENAL AGING, RENAL CELL CARCINOMA, RENAL FIBROSIS, CHRONIC KIDNEY DISEASE, POLYCYSTIC KIDNEY DISEASE, GLOMERULAR PODOCYTE INJURY, AND DIABETIC NEPHROPATHY. THESE STUDIES REVEAL THE DISTINCT CHARACTERS OF HDAC3 ABERRATIONS THAT ACT ON DIFFERENT MOLECULES/SIGNALING PATHWAYS UNDER VARIOUS RENAL PATHOLOGICAL CONDITIONS, WHICH MIGHT SHED LIGHTS INTO THE EPIGENETIC MECHANISMS OF RENAL DISEASES AND THE POTENTIALLY THERAPEUTIC STRATEGIES. 2022 17 1487 33 DNA DAMAGE AND EPIGENETIC CHANGES IN KIDNEY DISEASES - FOCUSED ON TRANSCRIPTION FACTORS IN PODOCYTES. RECENTLY IT HAS BEEN SHOWN THAT EPIGENETIC MECHANISMS ARE INVOLVED IN INITIATION AND PROGRESSION OF CARIDIOVASCULAR AND METABOLIC DISEASES, INCLUDING DIABETES, OBESITY, ATHEROSCLEROSIS, HEART FAILURE, HYPERTENSION AND KIDNEY DISEASES. IN THESE CHRONIC DISEASES, VARIOUS EXOGENOUS AND ENDOGENOUS STRESSES CAUSE DNA DAMAGE, FOLLOWED BY DNA REPAIR PROCESS. ACCUMULATION OF DNA DAMAGES AND IMPAIRED REPAIR PROCESS CAN LEAD TO EPIGENETIC CHANGES, WHICH MAY CONTRIBUTE TO ONSET AND PROGRESSION OF DISEASES. RECENTLY WE HAVE SHOWN THAT THERAPEUTIC EFFECT OF TRANSCRIPTION FACTOR KLF4 (KRUPPEL-LIKE FACTOR 4) IN KIDNEY GLOMERULAR EPITHELIAL CELLS (PODOCYTES) ON PROTEINURIC KIDNEY DISEASES THROUGH EPIGENETIC MECHANISMS. OUR RESULT SUGGESTS THE POSSIBILITY OF TRANSCRIPTION FACTORS AS A TARGET OF SELECTIVE EPIGENETIC THERAPY. MOREOVER, WE HAVE REPORTED THAT RENIN-ANGIOTENSIN SYSTEM (RAS) BLOCKERS, WHICH ARE WIDELY PRESCRIBED FOR THE TREATMENT OF CARDIOVASCULAR DISEASES, CAN RESTORE EPIGENETIC CHANGES THROUGH KLF4 IN PART. THESE RESULTS SUGGEST THAT ACTIVATION OF RAS CAUSES EPIGENETIC CHANGES IN DISEASE STATES, AND ELUCIDATION OF THE PRECISE MECHANISM MAY LEAD TO ESTABLISHMENT OF NOVEL THERAPEUTIC TARGET OF KIDNEY DISEASES. IN THIS REVIEW WE FOCUS ON DNA DAMAGE REPAIR SYSTEM AND EPIGENETIC MODULATORS IN DISEASE STATES, AND SPECULATE A CANDIDATE FOR EPIGENETIC THERAPY OF KIDNEY DISEASES. 2016 18 4974 27 PATHOPHYSIOLOGICAL MECHANISMS LEADING TO MUSCLE LOSS IN CHRONIC KIDNEY DISEASE. LOSS OF MUSCLE PROTEINS IS A DELETERIOUS CONSEQUENCE OF CHRONIC KIDNEY DISEASE (CKD) THAT CAUSES A DECREASE IN MUSCLE STRENGTH AND FUNCTION, AND CAN LEAD TO A REDUCTION IN QUALITY OF LIFE AND INCREASED RISK OF MORBIDITY AND MORTALITY. THE EFFECTIVENESS OF CURRENT TREATMENT STRATEGIES IN PREVENTING OR REVERSING MUSCLE PROTEIN LOSSES IS LIMITED. THE LIMITATIONS LARGELY STEM FROM THE SYSTEMIC NATURE OF DISEASES SUCH AS CKD, WHICH STIMULATE SKELETAL MUSCLE PROTEIN DEGRADATION PATHWAYS WHILE SIMULTANEOUSLY ACTIVATING MECHANISMS THAT IMPAIR MUSCLE PROTEIN SYNTHESIS AND REPAIR. STIMULI THAT INITIATE MUSCLE PROTEIN LOSS INCLUDE METABOLIC ACIDOSIS, INSULIN AND IGF1 RESISTANCE, CHANGES IN HORMONES, CYTOKINES, INFLAMMATORY PROCESSES AND DECREASED APPETITE. A GROWING BODY OF EVIDENCE SUGGESTS THAT SIGNALLING MOLECULES SECRETED FROM MUSCLE CAN ENTER THE CIRCULATION AND SUBSEQUENTLY INTERACT WITH RECIPIENT ORGANS, INCLUDING THE KIDNEYS, WHILE CONVERSELY, PATHOLOGICAL EVENTS IN THE KIDNEY CAN ADVERSELY INFLUENCE PROTEIN METABOLISM IN SKELETAL MUSCLE, DEMONSTRATING THE EXISTENCE OF CROSSTALK BETWEEN KIDNEY AND MUSCLE. TOGETHER, THESE SIGNALS, WHETHER DIRECT OR INDIRECT, INDUCE CHANGES IN THE LEVELS OF REGULATORY AND EFFECTOR PROTEINS VIA ALTERATIONS IN MRNAS, MICRORNAS AND CHROMATIN EPIGENETIC RESPONSES. ADVANCES IN OUR UNDERSTANDING OF THE SIGNALS AND PROCESSES THAT MEDIATE MUSCLE LOSS IN CKD AND OTHER MUSCLE WASTING CONDITIONS WILL SUPPORT THE FUTURE DEVELOPMENT OF THERAPEUTIC STRATEGIES TO REDUCE MUSCLE LOSS. 2022 19 5933 44 TARGETING EPIGENETICS AND NON-CODING RNAS IN ATHEROSCLEROSIS: FROM MECHANISMS TO THERAPEUTICS. ATHEROSCLEROSIS, THE PRINCIPAL CAUSE OF CARDIOVASCULAR DEATH WORLDWIDE, IS A PATHOLOGICAL DISEASE CHARACTERIZED BY FIBRO-PROLIFERATION, CHRONIC INFLAMMATION, LIPID ACCUMULATION, AND IMMUNE DISORDER IN THE VESSEL WALL. AS THE ATHEROMATOUS PLAQUES DEVELOP INTO ADVANCED STAGE, THE VULNERABLE PLAQUES ARE PRONE TO RUPTURE, WHICH CAUSES ACUTE CARDIOVASCULAR EVENTS, INCLUDING ISCHEMIC STROKE AND MYOCARDIAL INFARCTION. EMERGING EVIDENCE HAS SUGGESTED THAT ATHEROSCLEROSIS IS ALSO AN EPIGENETIC DISEASE WITH THE INTERPLAY OF MULTIPLE EPIGENETIC MECHANISMS. THE EPIGENETIC BASIS OF ATHEROSCLEROSIS HAS TRANSFORMED OUR KNOWLEDGE OF EPIGENETICS FROM AN IMPORTANT BIOLOGICAL PHENOMENON TO A BURGEONING FIELD IN CARDIOVASCULAR RESEARCH. HERE, WE PROVIDE A SYSTEMATIC AND UP-TO-DATE OVERVIEW OF THE CURRENT KNOWLEDGE OF THREE DISTINCT BUT INTERRELATED EPIGENETIC PROCESSES (INCLUDING DNA METHYLATION, HISTONE METHYLATION/ACETYLATION, AND NON-CODING RNAS), IN ATHEROSCLEROTIC PLAQUE DEVELOPMENT AND INSTABILITY. MECHANISTIC AND CONCEPTUAL ADVANCES IN UNDERSTANDING THE BIOLOGICAL ROLES OF VARIOUS EPIGENETIC MODIFIERS IN REGULATING GENE EXPRESSION AND FUNCTIONS OF ENDOTHELIAL CELLS (VASCULAR HOMEOSTASIS, LEUKOCYTE ADHESION, ENDOTHELIAL-MESENCHYMAL TRANSITION, ANGIOGENESIS, AND MECHANOTRANSDUCTION), SMOOTH MUSCLE CELLS (PROLIFERATION, MIGRATION, INFLAMMATION, HYPERTROPHY, AND PHENOTYPIC SWITCH), AND MACROPHAGES (DIFFERENTIATION, INFLAMMATION, FOAM CELL FORMATION, AND POLARIZATION) ARE DISCUSSED. THE INHERENTLY DYNAMIC NATURE AND REVERSIBILITY OF EPIGENETIC REGULATION, ENABLES THE POSSIBILITY OF EPIGENETIC THERAPY BY TARGETING EPIGENETIC "WRITERS", "READERS", AND "ERASERS". SEVERAL FOOD DRUG ADMINISTRATION-APPROVED SMALL-MOLECULE EPIGENETIC DRUGS SHOW PROMISE IN PRE-CLINICAL STUDIES FOR THE TREATMENT OF ATHEROSCLEROSIS. FINALLY, WE DISCUSS POTENTIAL THERAPEUTIC IMPLICATIONS AND CHALLENGES FOR FUTURE RESEARCH INVOLVING CARDIOVASCULAR EPIGENETICS, WITH AN AIM TO PROVIDE A TRANSLATIONAL PERSPECTIVE FOR IDENTIFYING NOVEL BIOMARKERS OF ATHEROSCLEROSIS, AND TRANSFORMING PRECISION CARDIOVASCULAR RESEARCH AND DISEASE THERAPY IN MODERN ERA OF EPIGENETICS. 2019 20 3826 41 INVESTIGATION OF EPIGENETICS IN KIDNEY CELL BIOLOGY. EPIGENETICS IS THE STUDY OF HERITABLE CHANGES IN DNA OR ITS ASSOCIATED PROTEINS EXCEPT MUTATIONS IN GENE SEQUENCE. EPIGENETIC REGULATION PLAYS FUNDAMENTAL ROLES IN THE PROCESSES OF KIDNEY CELL BIOLOGY THROUGH THE ACTION OF DNA METHYLATION, CHROMATIN MODIFICATIONS VIA EPIGENETIC REGULATORS AND INTERACTION VIA TRANSCRIPTION FACTORS, AND NONCODING RNA SPECIES. KIDNEY DISEASES, INCLUDING ACUTE KIDNEY INJURY, CHRONIC KIDNEY DISEASE, NEPHRITIC AND NEPHROTIC SYNDROMES, PYELONEPHRITIS AND POLYCYSTIC KIDNEY DISEASES ARE DRIVEN BY ABERRANT ACTIVITY IN NUMEROUS SIGNALING PATHWAYS IN EVEN INDIVIDUAL KIDNEY CELL. EPIGENETIC ALTERATIONS, INCLUDING DNA METHYLATION, HISTONE ACETYLATION AND METHYLATION, NONCODING RNAS, AND PROTEIN POSTTRANSLATIONAL MODIFICATIONS, COULD DISRUPT ESSENTIAL PATHWAYS THAT PROTECT THE RENAL CELLS FROM UNCONTROLLED GROWTH, APOPTOSIS AND ESTABLISHMENT OF OTHER RENAL ASSOCIATED SYNDROMES, WHICH HAVE BEEN RECOGNIZED AS ONE OF THE CRITICAL MECHANISMS FOR REGULATING FUNCTIONAL CHANGES THAT DRIVE AND MAINTAIN THE KIDNEY DISEASE PHENOTYPE. IN THIS CHAPTER, WE BRIEFLY SUMMARIZE THE EPIGENETIC MECHANISMS IN KIDNEY CELL BIOLOGY AND EPIGENETIC BASIS OF KIDNEY DEVELOPMENT, AND INTRODUCE EPIGENETIC TECHNIQUES THAT CAN BE USED IN INVESTIGATING THE MOLECULAR MECHANISM OF KIDNEY CELL BIOLOGY AND KIDNEYS DISEASES, PRIMARILY FOCUSING ON THE INTEGRATION OF DNA METHYLATION AND CHROMATIN IMMUNOPRECIPITATION TECHNOLOGIES INTO KIDNEY DISEASE ASSOCIATED STUDIES. FUTURE STUDIES USING THESE EMERGING TECHNOLOGIES WILL ELUCIDATE HOW ALTERATIONS IN THE RENAL CELL EPIGENOME COOPERATE WITH GENETIC ABERRATIONS FOR KIDNEY DISEASE INITIATION AND PROGRESSION. INCORPORATING EPIGENOMIC TESTING INTO THE CLINICAL RESEARCH IS ESSENTIAL TO FUTURE STUDIES WITH EPIGENETICS BIOMARKERS AND PRECISION MEDICINE USING EMERGING EPIGENETIC THERAPIES. 2019