1 3452 110 HYPERTENSIVE DISORDERS OF PREGNANCY SHARE COMMON CFDNA METHYLATION PROFILES. HYPERTENSIVE DISORDERS OF PREGNANCY (HDP) CONTRIBUTE SUBSTANTIALLY TO PERINATAL MORBIDITY AND MORTALITY. EPIGENETIC CHANGES POINT TOWARDS CARDIO-METABOLIC DYSREGULATION FOR THESE VASCULAR DISORDERS. IN EARLY PREGNANCY, EPIGENETIC CHANGES USING CELL FREE DNA (CFDNA) ARE LARGELY UNEXPLORED. WE AIMED TO INVESTIGATE THESE IN HDP BETWEEN 11 AND 14 WEEKS OF GESTATION BY ANALYSIS OF CFDNA METHYLATION PROFILES IN PATIENTS WITH HYPERTENSIVE DISORDERS. WE IDENTIFIED PATIENTS WITHOUT CHRONIC HYPERTENSION BUT WITH SUBSEQUENT DEVELOPMENT OF PREECLAMPSIA (PE) (N = 11), WITH CHRONIC HYPERTENSION (HT) BUT WITHOUT PE DEVELOPMENT (N = 14), AND LACKING BOTH PE AND HT (N = 422). WE MATCHED PATIENTS ACCORDING TO PE RISK FACTORS INTO THREE GROUPS (N = 5 EACH GROUP): (1) PE: NO HT BUT PE DEVELOPMENT, (2) HT: CHRONIC HYPERTENSION BUT NO PE AND (3) CONTROL: NO PE OR HT. WE SUCCESSFULLY OPTIMIZED OUR CFDNA ISOLATION PROCESS PRIOR TO WHOLE GENOME BISULFITE SEQUENCING. ANALYSIS OF CFDNA METHYLATION CHANGES INDICATE A COMMON PREDISPOSITION IN PE AND HT GROUPS, CHIEFLY OF MATERNAL ORIGIN. ASSESSMENT OF SIGNIFICANT DIFFERENTIALLY METHYLATED REGIONS AND ANNOTATED GENES POINT TOWARDS A COMMON CARDIOVASCULAR PREDISPOSITION IN PREECLAMPSIA AND HYPERTENSION GROUPS IN THE FIRST TRIMESTER. WE POSTULATE THE PIVOTAL ROLE OF THE MATERNAL CARDIOVASCULAR SYSTEM IN HDP, WHICH IS ALREADY EVIDENT IN THE FIRST TRIMESTER. 2022 2 4065 30 MATERNAL AND GESTATIONAL INFLUENCES ON CHILDHOOD BLOOD PRESSURE. EXPOSURES THAT CONTRIBUTE TO A SUB-OPTIMAL INTRAUTERINE ENVIRONMENT CAN HAVE AN EFFECT ON THE DEVELOPING FETUS. IMPAIRED FETAL GROWTH THAT RESULTS IN LOW BIRTH WEIGHT IS AN ESTABLISHED RISK FACTOR FOR CARDIO-METABOLIC DISORDERS LATER IN LIFE. RECENT EPIDEMIOLOGIC AND PROSPECTIVE COHORT STUDIES THAT INCLUDE THE MATERNAL AND GESTATIONAL PERIOD HAVE IDENTIFIED MATERNAL AND GESTATIONAL CONDITIONS THAT CONFER INCREASED RISK FOR SUBSEQUENT CARDIO-METABOLIC DISORDERS IN THE ABSENCE OF LOW BIRTH WEIGHT. MATERNAL PRE-CONCEPTION HEALTH STATUS, INCLUDING CHRONIC OBESITY AND TYPE 2 DIABETES, INCREASE RISK FOR CHILDHOOD OBESITY AND OBESITY-RELATED HIGHER BLOOD PRESSURE (BP) IN CHILD OFFSPRING. MATERNAL GESTATIONAL EXPOSURES, INCLUDING GESTATIONAL DIABETES, GESTATIONAL HYPERTENSION, AND PREECLAMPSIA, ARE ASSOCIATED WITH HIGHER BP IN OFFSPRING. OTHER MATERNAL EXPOSURES SUCH AS CIGARETTE SMOKE AND AIR POLLUTION ALSO INCREASE RISK FOR HIGHER BP IN CHILD OFFSPRING. RECENT, BUT LIMITED, DATA INDICATE THAT ASSISTED REPRODUCTIVE TECHNOLOGIES CAN BE ASSOCIATED WITH HYPERTENSION IN CHILDHOOD, DESPITE OTHERWISE NORMAL GESTATION AND HEALTHY NEWBORN. GESTATIONAL EXPOSURES ASSOCIATED WITH HIGHER BP IN CHILDHOOD CAN BE RELATED TO FAMILIAL LIFESTYLE FACTORS, GENETICS, OR EPIGENETIC MODIFICATION OF FETAL DEOXYRIBONUCLEIC ACID (DNA). THESE FACTORS, OR COMBINATION OF FACTORS, AS WELL AS OTHER ADVERSE INTRAUTERINE CONDITIONS, COULD INDUCE FETAL PROGRAMING LEADING TO HEALTH CONSEQUENCES IN LATER LIFE. CURRENT AND DEVELOPING RESEARCH WILL PROVIDE ADDITIONAL INSIGHTS ON GESTATIONAL EXPOSURES AND FETAL ADJUSTMENTS THAT INCREASE RISK FOR HIGHER BP LEVELS IN CHILDHOOD. 2020 3 1392 29 DIAGNOSTIC APPROACH TO PULMONARY HYPERTENSION IN PREMATURE NEONATES. BRONCHOPULMONARY DYSPLASIA (BPD) IS A FORM OF CHRONIC LUNG DISEASE IN PREMATURE INFANTS FOLLOWING RESPIRATORY DISTRESS AT BIRTH. WITH INCREASING SURVIVAL OF EXTREMELY LOW BIRTH WEIGHT INFANTS, ALVEOLAR SIMPLIFICATION IS THE DEFINING LUNG CHARACTERISTIC OF INFANTS WITH BPD, AND ALONG WITH PULMONARY HYPERTENSION, INCREASINGLY CONTRIBUTES TO BOTH RESPIRATORY MORBIDITY AND MORTALITY IN THESE INFANTS. GROWTH RESTRICTED INFANTS, INFANTS BORN TO MOTHERS WITH OLIGOHYDRAMNIOS OR FOLLOWING PROLONGED PRETERM RUPTURE OF MEMBRANES ARE AT PARTICULAR RISK FOR EARLY ONSET PULMONARY HYPERTENSION. ALTERED VASCULAR AND ALVEOLAR GROWTH PARTICULARLY IN CANALICULAR AND EARLY SACCULAR STAGES OF LUNG DEVELOPMENT FOLLOWING MECHANICAL VENTILATION AND OXYGEN THERAPY, RESULTS IN DEVELOPMENTAL LUNG ARREST LEADING TO BPD WITH PULMONARY HYPERTENSION (PH). EARLY RECOGNITION OF PH IN INFANTS WITH RISK FACTORS IS IMPORTANT FOR OPTIMAL MANAGEMENT OF THESE INFANTS. SCREENING TOOLS FOR EARLY DIAGNOSIS OF PH ARE EVOLVING; HOWEVER, ECHOCARDIOGRAPHY IS THE MAINSTAY FOR NON-INVASIVE DIAGNOSIS OF PH IN INFANTS. CARDIAC COMPUTED TOMOGRAPHY (CT) AND MAGNETIC RESONANCE ARE BEING USED AS IMAGING MODALITIES, HOWEVER THEIR ROLE IN IMPROVING OUTCOMES IN THESE PATIENTS IS UNCERTAIN. FOLLOW-UP OF INFANTS AT RISK FOR PH WILL HELP NOT ONLY IN EARLY DIAGNOSIS, BUT ALSO IN APPROPRIATE MANAGEMENT OF THESE INFANTS. AGGRESSIVE MANAGEMENT OF LUNG DISEASE, AVOIDANCE OF HYPOXEMIC EPISODES, AND OPTIMAL NUTRITION DETERMINE THE PROGRESSION OF PH, AS EPIGENETIC FACTORS MAY HAVE SIGNIFICANT EFFECTS, PARTICULARLY IN GROWTH-RESTRICTED INFANTS. INFANTS WITH DIAGNOSIS OF PH ARE MANAGED WITH PULMONARY VASODILATORS AND THOSE RESISTANT TO THERAPY NEED TO BE WORKED UP FOR THE PRESENCE OF CARDIO-VASCULAR ANOMALIES. THE MANAGEMENT OF INFANTS AND TODDLERS WITH PH, ESPECIALLY FOLLOWING PREMATURE BIRTH IS AN EMERGING FIELD. NONETHELESS, COMBINATION THERAPIES IN A MULTI-DISCIPLINARY SETTING IMPROVES OUTCOMES FOR THESE INFANTS. 2017 4 5174 23 PREDICTIVE AND PROGNOSTIC BIOMARKERS OF RESPIRATORY DISEASES DUE TO PARTICULATE MATTER EXPOSURE. AIR POLLUTION IS GETTING SEVERE AND CONCERNS ABOUT ITS TOXICITY EFFECTS ON AIRWAY AND LUNG DISEASE ARE ALSO INCREASING. PARTICULATE MATTER (PM) IS MAJOR COMPONENT OF AIR POLLUTANT. IT CAUSES RESPIRATORY DISEASES, SUCH AS ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, LUNG CANCER, AND SO ON. PM PARTICLES ENTER THE AIRWAY AND LUNG BY INHALATION, CAUSING DAMAGES TO THEM. ESPECIALLY, PM(2.5) CAN PENETRATE INTO THE ALVEOLUS AND PASS TO THE SYSTEMIC CIRCULATION. IT CAN AFFECT THE CARDIOPULMONARY SYSTEM AND CAUSE CARDIOPULMONARY DISORDERS. IN THIS REVIEW, WE FOCUSED ON PM-INDUCING TOXICITY MECHANISMS IN THE FRAMEWORK OF OXIDATIVE STRESS, INFLAMMATION, AND EPIGENETIC CHANGES. WE ALSO REVIEWED ITS CORRELATION WITH RESPIRATORY DISEASES. IN ADDITION, WE REVIEWED BIOMARKERS RELATED TO PM-INDUCED RESPIRATORY DISEASES. THESE BIOMARKERS MIGHT BE USED FOR DISEASE PREDICTION AND EARLY DIAGNOSIS. WITH RECENT TREND OF USING GENOMIC ANALYSIS TOOLS IN THE FIELD OF TOXICOGENOMICS, RESPIRATORY DISEASE BIOMARKERS ASSOCIATED WITH PM WILL BE CONTINUOUSLY INVESTIGATED. EFFECTIVE BIOMARKERS DERIVED FROM EARLIER STUDIES AND FURTHER STUDIES MIGHT BE UTILIZED TO REDUCE RESPIRATORY DISEASES. 2017 5 5048 26 PHARMACOLOGICAL APPROACHES IN EITHER INTERMITTENT OR PERMANENT HYPOXIA: A TALE OF TWO EXPOSURES. HYPOXIA INDUCES SEVERAL RESPONSES AT CARDIOVASCULAR, PULMONARY AND REPRODUCTIVE LEVELS, WHICH MAY LEAD TO CHRONIC DISEASES. THIS IS RELEVANT IN HUMAN POPULATIONS EXPOSED TO HIGH ALTITUDE (HA), IN EITHER CHRONIC CONTINUOUS (PERMANENT INHABITANTS) OR INTERMITTENT FASHION (HA WORKERS, TOURISTS AND MOUNTAINEERS). IN CHILE, IT IS ESTIMATED THAT 1.000.000 PEOPLE LIVE AT HIGHLANDS AND MORE THAN 55.000 WORK IN HA SHIFTS. INITIAL RESPONSES TO HYPOXIA ARE COMPENSATORY AND INDUCE ACTIVATION OF CARDIOPROTECTIVE MECHANISMS, SUCH AS THOSE SEEN UNDER INTERMITTENT HYPOBARIC (IH) HYPOXIA, EVENTS THAT COULD MEDIATE PRECONDITIONING. HOWEVER, WHENEVER HYPOXIA IS PROLONGED, THE CHRONIC ACTIVATION OF CELLULAR RESPONSES INDUCES LONG-LASTING MODIFICATIONS THAT MAY RESULT IN ACCLIMATIZATION OR PRODUCE MALADAPTIVE CHANGES WITH INCREASE IN CARDIOVASCULAR RISK. HA EXPOSURE DURING PREGNANCY INDUCES HYPOXIA AND OXIDATIVE STRESS, WHICH IN TURN MAY PROMOTE CELLULAR RESPONSES AND EPIGENETIC MODIFICATIONS RESULTING IN SEVERE IMPAIRMENT IN GROWTH AND DEVELOPMENT. SADLY, THIS CONDITION IS ACCOMPANIED WITH AN INCREASED FETAL AND NEONATAL MORBI-MORTALITY. FURTHER, DEVELOPMENTAL HYPOXIA MAY PROGRAM CARDIO-PULMONARY CIRCULATIONS LATER IN POSTNATAL LIFE, ENDING IN VASCULAR STRUCTURAL AND FUNCTIONAL ALTERATIONS WITH AUGMENTED RISK ON PULMONARY AND CARDIOVASCULAR FAILURE. ADDITIONALLY, PERMANENT HA INHABITANTS HAVE AUGMENTED RISK AND PREVALENCE OF CHRONIC HYPOXIC PULMONARY HYPERTENSION, RIGHT VENTRICULAR HYPERTROPHY AND CARDIOPULMONARY REMODELING. SIMILAR RESPONSES ARE SEEN IN ADULTS THAT ARE INTERMITTENTLY EXPOSED TO CHRONIC HYPOXIA (CH) SUCH AS SHIFT WORKERS IN HA AREAS. THE MECHANISMS INVOLVED DETERMINING THE IMMEDIATE, SHORT AND LONG-LASTING EFFECTS ARE STILL UNCLEAR. FOR SEVERAL YEARS, THE STUDY OF THE RESPONSES TO HYPOXIC INSULTS AND PHARMACOLOGICAL TARGETS HAS BEEN THE MOTIVATION OF OUR GROUP. THIS REVIEW DESCRIBES SOME OF THE MECHANISMS UNDERLYING HYPOXIC RESPONSES AND POTENTIAL THERAPEUTIC APPROACHES WITH ANTIOXIDANTS SUCH AS MELATONIN, ASCORBATE, OMEGA 3 (OMEGA3) OR COMPOUNDS THAT INCREASE THE NITRIC OXIDE (NO) BIOAVAILABILITY. 2015 6 496 27 ASSESSMENT OF THE IMPACT OF HIV INFECTION AND ANTI-RETROVIRAL TREATMENT ON THE CARDIOMETABOLIC HEALTH OF PREGNANT MOTHERS AND THEIR OFFSPRING (ARTMOMSBABES). BACKGROUND: THE RISK OF CARDIOVASCULAR DISEASES (CVDS) IS BECOMING MORE PREVALENT IN PREGNANT WOMEN THOUGH NOT MUCH DATA IS AVAILABLE FOR PREGNANT WOMEN WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV). FOETOPLACENTAL VASCULAR ENDOTHELIAL DYSFUNCTION IS THOUGHT TO BE AT THE ORIGIN OF CHRONIC DISEASES SUCH AS DIABETES AND OBESITY LATER ON IN LIFE. BECAUSE HIV AND ANTI-RETROVIRAL TREATMENT (ARTS) ARE ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION, CHILDREN EXPOSED IN UTERO TO THESE CONDITIONS MAY BE AT GREATER RISK OF DEVELOPING CVDS. DESPITE THE HIGH PREVALENCE OF HIV IN PREGNANT SOUTH AFRICAN WOMEN, LITTLE IS KNOWN ABOUT THE EFFECTS OF ART ON THE CARDIOVASCULAR HEALTH OF THE MOTHER AND OFFSPRING. HENCE, THE PROPOSED STUDY INTENDS TO INVESTIGATE HOW HIV/ARTS MAY AFFECT THE CARDIOVASCULAR HEALTH OF THE MOTHER AND OFFSPRING AT DIFFERENT TIME POINTS DURING THE PREGNANCY AND UP TO 2 YEARS AFTER BIRTH. METHODS: A LONGITUDINAL CASE-CONTROL STUDY IN HIV POSITIVE PREGNANT WOMEN ON ART AND HIV NEGATIVE PREGNANT WOMEN WILL BE CONDUCTED. ALL PREGNANT WOMEN WILL BE ASSESSED FOR CARDIO-METABOLIC RISK FACTORS AND MARKERS (LIPIDS, ANTHROPOMETRIC AND GLYCAEMIC INDIES, OXIDATIVE STRESS), HEMODYNAMIC STATUS (BLOOD PRESSURE PARAMETERS) AND VASCULAR FUNCTION (ARTERIAL COMPLIANCE, RETINAL MICROVASCULATURE, UTERINE ARTERY MEAN PULSATILITY INDEX). CHILD HEALTH WILL BE MONITORED IN UTERO AND POSTNATALLY VIA ROUTINE FOETAL HEALTH SCREENING, PLACENTAL INTEGRITY, ANTHROPOMETRY, BLOOD PRESSURE PARAMETERS, MARKERS OF OXIDATIVE STRESS AND ENDOTHELIAL FUNCTION IN CORD BLOOD AND CARDIOVASCULAR EPIGENETIC MARKERS IN URINE. DISCUSSION: THERE IS A PAUCITY OF STUDIES IN SOUTH AFRICA AND SUB-SAHARA AFRICA AS A WHOLE THAT UTILISED A LONGITUDINAL STUDY MODEL TO ASSESS THE EFFECTS OF ARTS ON VASCULAR ENDOTHELIAL CHANGES IN PREGNANT WOMEN LIVING WITH HIV AND THE CARDIOMETABOLIC HEALTH OF THEIR OFFSPRING. THIS STUDY WILL THEREFORE HELP TO MONITOR CHANGES IN CARDIOMETABOLIC RISK DURING PREGNANCY AND IN CHILDREN EXPOSED IN UTERO TO HIV-INFECTION AND ART USE. FINDINGS FROM THIS STUDY WILL PROVIDE USEFUL INFORMATION FOR DEVELOPING GUIDELINES ON THE USE OF ARTS IN PREGNANCY AND MANAGEMENT OF CARDIOMETABOLIC HEALTH OF THE OFFSPRING OF HIV POSITIVE MOTHERS. 2021 7 1157 22 CONTAMINANT METALS AS CARDIOVASCULAR RISK FACTORS: A SCIENTIFIC STATEMENT FROM THE AMERICAN HEART ASSOCIATION. EXPOSURE TO ENVIRONMENTAL POLLUTANTS IS LINKED TO INCREASED RISK OF CARDIOVASCULAR DISEASE. BEYOND THE EXTENSIVE EVIDENCE FOR PARTICULATE AIR POLLUTION, ACCUMULATING EVIDENCE SUPPORTS THAT EXPOSURE TO NONESSENTIAL METALS SUCH AS LEAD, CADMIUM, AND ARSENIC IS A SIGNIFICANT CONTRIBUTOR TO CARDIOVASCULAR DISEASE WORLDWIDE. HUMANS ARE EXPOSED TO METALS THROUGH AIR, WATER, SOIL, AND FOOD AND EXTENSIVE INDUSTRIAL AND PUBLIC USE. CONTAMINANT METALS INTERFERE WITH CRITICAL INTRACELLULAR REACTIONS AND FUNCTIONS LEADING TO OXIDATIVE STRESS AND CHRONIC INFLAMMATION THAT RESULT IN ENDOTHELIAL DYSFUNCTION, HYPERTENSION, EPIGENETIC DYSREGULATION, DYSLIPIDEMIA, AND CHANGES IN MYOCARDIAL EXCITATION AND CONTRACTILE FUNCTION. LEAD, CADMIUM, AND ARSENIC HAVE BEEN LINKED TO SUBCLINICAL ATHEROSCLEROSIS, CORONARY ARTERY STENOSIS, AND CALCIFICATION AS WELL AS TO INCREASED RISK OF ISCHEMIC HEART DISEASE AND STROKE, LEFT VENTRICULAR HYPERTROPHY AND HEART FAILURE, AND PERIPHERAL ARTERY DISEASE. EPIDEMIOLOGICAL STUDIES SHOW THAT EXPOSURE TO LEAD, CADMIUM, OR ARSENIC IS ASSOCIATED WITH CARDIOVASCULAR DEATH MOSTLY ATTRIBUTABLE TO ISCHEMIC HEART DISEASE. PUBLIC HEALTH MEASURES REDUCING METAL EXPOSURE ARE ASSOCIATED WITH REDUCTIONS IN CARDIOVASCULAR DISEASE DEATH. POPULATIONS OF COLOR AND LOW SOCIOECONOMIC MEANS ARE MORE COMMONLY EXPOSED TO METALS AND THEREFORE AT GREATER RISK OF METAL-INDUCED CARDIOVASCULAR DISEASE. TOGETHER WITH STRENGTHENING PUBLIC HEALTH MEASURES TO PREVENT METAL EXPOSURES, DEVELOPMENT OF MORE SENSITIVE AND SELECTIVE MEASUREMENT MODALITIES, CLINICAL MONITORING OF METAL EXPOSURES, AND THE DEVELOPMENT OF METAL CHELATION THERAPIES COULD FURTHER DIMINISH THE BURDEN OF CARDIOVASCULAR DISEASE ATTRIBUTABLE TO METAL EXPOSURE. 2023 8 361 25 AMBIENT AIR POLLUTION AND THROMBOSIS. AIR POLLUTION IS A GROWING PUBLIC HEALTH CONCERN OF GLOBAL SIGNIFICANCE. ACUTE AND CHRONIC EXPOSURE IS KNOWN TO IMPAIR CARDIOVASCULAR FUNCTION, EXACERBATE DISEASE AND INCREASE CARDIOVASCULAR MORTALITY. SEVERAL PLAUSIBLE BIOLOGICAL MECHANISMS HAVE BEEN PROPOSED FOR THESE ASSOCIATIONS, HOWEVER, AT PRESENT, THE PATHWAYS ARE INCOMPLETE. A SEMINAL REVIEW BY THE AMERICAN HEART ASSOCIATION (2010) CONCLUDED THAT THE THROMBOTIC EFFECTS OF PARTICULATE AIR POLLUTION LIKELY CONTRIBUTED TO THEIR EFFECTS ON CARDIOVASCULAR MORTALITY AND MORBIDITY. THE AIM OF THE CURRENT REVIEW IS TO APPRAISE THE NEWLY ACCUMULATED SCIENTIFIC EVIDENCE (2009-2016) ON CONTRIBUTION OF HAEMOSTASIS AND THROMBOSIS TOWARDS CARDIOVASCULAR DISEASE INDUCED BY EXPOSURE TO BOTH PARTICULATE AND GASEOUS POLLUTANTS.SEVENTY FOUR PUBLICATIONS WERE REVIEWED IN-DEPTH. THE WEIGHT OF EVIDENCE SUGGESTS THAT ACUTE EXPOSURE TO FINE PARTICULATE MATTER (PM(2.5)) INDUCES A SHIFT IN THE HAEMOSTATIC BALANCE TOWARDS A PRO-THROMBOTIC/PRO-COAGULATIVE STATE. INSUFFICIENT DATA WAS AVAILABLE TO ASCERTAIN IF A SIMILAR RELATIONSHIP EXISTS FOR GASEOUS POLLUTANTS, AND VERY FEW STUDIES HAVE ADDRESSED LONG-TERM EXPOSURE TO AMBIENT AIR POLLUTION. PLATELET ACTIVATION, OXIDATIVE STRESS, INTERPLAY BETWEEN INTERLEUKIN-6 AND TISSUE FACTOR, ALL APPEAR TO BE POTENTIALLY IMPORTANT MECHANISMS IN POLLUTION-MEDIATED THROMBOSIS, TOGETHER WITH AN EMERGING ROLE FOR CIRCULATING MICROVESICLES AND EPIGENETIC CHANGES.OVERALL, THE RECENT LITERATURE SUPPORTS, AND ARGUABLY STRENGTHENS, THE CONTENTION THAT AIR POLLUTION CONTRIBUTES TO CARDIOVASCULAR MORBIDITY BY PROMOTING HAEMOSTASIS. THE VOLUME AND DIVERSITY OF THE EVIDENCE HIGHLIGHTS THE COMPLEXITY OF THE PATHOPHYSIOLOGIC MECHANISMS BY WHICH AIR POLLUTION PROMOTES THROMBOSIS; MULTIPLE PATHWAYS ARE PLAUSIBLE AND IT IS MOST LIKELY THEY ACT IN CONCERT. FUTURE RESEARCH SHOULD ADDRESS THE ROLE GASEOUS POLLUTANTS PLAY IN THE CARDIOVASCULAR EFFECTS OF AIR POLLUTION MIXTURE AND DIRECT COMPARISON OF POTENTIALLY SUSCEPTIBLE GROUPS TO HEALTHY INDIVIDUALS. 2018 9 3975 36 LONG-TERM CONSEQUENCES OF PLACENTAL VASCULAR PATHOLOGY ON THE MATERNAL AND OFFSPRING CARDIOVASCULAR SYSTEMS. OVER THE LAST THIRTY YEARS, EVIDENCE HAS BEEN ACCUMULATING THAT HYPERTENSIVE DISORDERS OF PREGNANCY (HDP) AND, SPECIFICALLY, PREECLAMPSIA (PE) PRODUCE NOT ONLY LONG-TERM EFFECTS ON THE PREGNANT WOMAN, BUT HAVE ALSO LASTING CONSEQUENCES FOR THE FETUS. AT THE CORE OF THESE CONSEQUENCES IS THE PHENOMENON KNOWN AS DEFECTIVE DEEP PLACENTATION, BEING PRESENT IN VIRTUALLY EVERY MAJOR OBSTETRICAL SYNDROME. THE PROFOUND PLACENTAL VASCULAR LESIONS CHARACTERISTIC OF THIS PATHOLOGY CAN INDUCE LONG-TERM ADVERSE CONSEQUENCES FOR THE PREGNANT WOMAN'S ENTIRE ARTERIAL SYSTEM. IN ADDITION, PLACENTAL GROWTH RESTRICTION AND FUNCTION CAN, IN TURN, CAUSE A DECREASED BLOOD SUPPLY TO THE FETUS, WITH LONG-LASTING EFFECTS. WOMEN WITH A HISTORY OF HDP HAVE AN INCREASED RISK OF CARDIOVASCULAR DISEASES (CVD) COMPARED WITH WOMEN WITH NORMAL PREGNANCIES. SPECIFICALLY, THESE SUBJECTS ARE AT A FUTURE HIGHER RISK OF: HYPERTENSION; CORONARY ARTERY DISEASE; HEART FAILURE; PERIPHERAL VASCULAR DISEASE; CEREBROVASCULAR ACCIDENTS (STROKE); CVD-RELATED MORTALITY. VASCULAR PATHOLOGY IN PREGNANCY AND CVD MAY SHARE A COMMON ETIOLOGY AND MAY HAVE COMMON RISK FACTORS, WHICH ARE UNMASKED BY THE "STRESS" OF PREGNANCY. IT IS ALSO POSSIBLE THAT THE FUTURE OCCURRENCE OF A CVD MAY BE THE CONSEQUENCE OF ENDOTHELIAL DYSFUNCTION GENERATED BY PREGNANCY-INDUCED HYPERTENSION THAT PERSISTS AFTER DELIVERY. ALTHOUGH BIOCHEMICAL AND BIOPHYSICAL MARKERS OF PE ABOUND, INFORMATION ON MARKERS FOR A COMPARATIVE EVALUATION IN THE VARIOUS GROUPS IS STILL LACKING. LONG-TERM CONSEQUENCES FOR THE FETUS ARE AN INTEGRAL PART OF THE THEORY OF A FETAL ORIGIN OF A NUMBER OF ADULT DISEASES, KNOWN AS THE BARKER HYPOTHESIS. INDEED, INTRAUTERINE MALNUTRITION AND FETAL GROWTH RESTRICTION REPRESENT SIGNIFICANT RISK FACTORS FOR THE DEVELOPMENT OF CHRONIC HYPERTENSION, DIABETES, STROKE AND DEATH FROM CORONARY ARTERY DISEASE IN ADULTS. OTHER FACTORS WILL ALSO INFLUENCE THE DEVELOPMENT LATER IN LIFE OF HYPERTENSION, CORONARY AND MYOCARDIAL DISEASE; THEY INCLUDE PARENTAL GENETIC DISPOSITION, EPIGENETIC MODIFICATIONS, ENDOTHELIAL DYSFUNCTION, CONCURRENT INTRAUTERINE EXPOSURES, AND THE LIFESTYLE OF THE AFFECTED INDIVIDUAL. 2021 10 1388 22 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE: NON-INVASIVE ASSESSMENT OF CARDIOVASCULAR RISK. THE PREVALENCE AND BURDEN OF DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE ON GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT IS ALREADY HEAVY AND STILL RISING. DIABETES MELLITUS BY ITSELF IS LINKED TO ADVERSE CARDIOVASCULAR EVENTS, AND THE PRESENCE OF CONCOMITANT CHRONIC KIDNEY DISEASE FURTHER AMPLIFIES CARDIOVASCULAR RISK. THE CULMINATION OF TRADITIONAL (MALE GENDER, SMOKING, ADVANCED AGE, OBESITY, ARTERIAL HYPERTENSION AND DYSLIPIDEMIA) AND NON-TRADITIONAL RISK FACTORS (ANEMIA, INFLAMMATION, PROTEINURIA, VOLUME OVERLOAD, MINERAL METABOLISM ABNORMALITIES, OXIDATIVE STRESS, ETC.) CONTRIBUTES TO ADVANCED ATHEROSCLEROSIS AND INCREASED CARDIOVASCULAR RISK. TO DECREASE THE MORBIDITY AND MORTALITY OF THESE PATIENTS DUE TO CARDIOVASCULAR CAUSES, TIMELY AND EFFICIENT CARDIOVASCULAR RISK ASSESSMENT IS OF HUGE IMPORTANCE. CARDIOVASCULAR RISK ASSESSMENT CAN BE BASED ON LABORATORY PARAMETERS, IMAGING TECHNIQUES, ARTERIAL STIFFNESS PARAMETERS, ANKLE-BRACHIAL INDEX AND 24 H BLOOD PRESSURE MEASUREMENTS. NEWER METHODS INCLUDE EPIGENETIC MARKERS, SOLUBLE ADHESION MOLECULES, CYTOKINES AND MARKERS OF OXIDATIVE STRESS. IN THIS REVIEW, THE AUTHORS PRESENT SEVERAL NON-INVASIVE METHODS OF CARDIOVASCULAR RISK ASSESSMENT IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE. 2021 11 2805 23 FETAL MALNUTRITION AND LONG-TERM OUTCOMES. EPIDEMIOLOGICAL STUDIES HAVE SHOWN THAT LOWER BIRTHWEIGHT IS ASSOCIATED WITH A WIDE RANGE OF ADVERSE OUTCOMES IN LATER LIFE, INCLUDING POORER 'HUMAN CAPITAL' (SHORTER STATURE, LOWER COGNITIVE PERFORMANCE), INCREASED RISK FACTORS FOR LATER DISEASE (HIGHER BLOOD PRESSURE AND REDUCED GLUCOSE TOLERANCE, AND LUNG, KIDNEY AND IMMUNE FUNCTION), CLINICAL DISEASE (DIABETES, CORONARY HEART DISEASE, CHRONIC LUNG AND KIDNEY DISEASE), AND INCREASED ALL-CAUSE AND CARDIOVASCULAR MORTALITY. HIGHER BIRTHWEIGHT IS ASSOCIATED WITH AN INCREASED RISK OF CANCER AND (IF CAUSED BY GESTATIONAL DIABETES) OBESITY AND DIABETES. THE 'DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE' HYPOTHESIS PROPOSES THAT FETAL NUTRITION HAS PERMANENT EFFECTS ON GROWTH, STRUCTURE AND METABOLISM ('PROGRAMMING'). THIS IS SUPPORTED BY STUDIES IN ANIMALS SHOWING THAT MATERNAL UNDER- AND OVERNUTRITION DURING PREGNANCY CAN PRODUCE SIMILAR ABNORMALITIES IN THE ADULT OFFSPRING. COMMON CHRONIC DISEASES COULD POTENTIALLY BE PREVENTED BY ACHIEVING OPTIMAL FETAL NUTRITION, AND THIS COULD HAVE ADDITIONAL BENEFITS FOR SURVIVAL AND HUMAN CAPITAL. RECENT FOLLOW-UP OF CHILDREN BORN AFTER RANDOMIZED NUTRITIONAL INTERVENTIONS IN PREGNANCY PROVIDES WEAK EVIDENCE OF BENEFICIAL EFFECTS ON GROWTH, VASCULAR FUNCTION, LIPID CONCENTRATIONS, GLUCOSE TOLERANCE AND INSULIN RESISTANCE. ANIMAL STUDIES INDICATE THAT EPIGENETIC PHENOMENA MAY BE AN IMPORTANT MECHANISM UNDERLYING PROGRAMMING, AND THAT NUTRITIONAL INTERVENTIONS MAY NEED TO START PRECONCEPTIONALLY. 2013 12 3099 27 GENOMIC DNA METHYLATION SIGNATURES IN DIFFERENT TISSUES AFTER AMBIENT AIR PARTICULATE MATTER EXPOSURE. DNA METHYLATION (5-MC) IS ONE OF THE SEVERAL EPIGENETIC MARKERS, AND IS GENERALLY ASSOCIATED WITH THE INHIBITION OF GENE EXPRESSION. BOTH HYPER AND HYPO DNA METHYLATION ARE ASSOCIATED WITH THE DISEASES. EXPOSURE TO FINE PARTICLES WITH A DIAMETER OF 2.5 MUM OR LESS (PM(2.5)) IS A PERVASIVE RISK FACTOR FOR CARDIOPULMONARY MORTALITY, METABOLIC DISORDERS, COGNITION DAMAGE, AND ETC.. RECENT REPORTS POINTED TOWARD THAT THESE DISEASES WERE ASSOCIATED WITH THE ALTERED DNA METHYLATION LEVEL OF SOME SPECIFIC-GENE, POTENTIALLY SUGGESTING THAT THE DNA METHYLATION ALTERATION WAS INVOLVED IN THE HEALTH HAZARD DERIVED FROM THE PM(2.5) EXPOSURE. IN THIS STUDY, WE SYSTEMATICALLY INVESTIGATED THE GLOBAL DNA METHYLATION LEVEL OF MOST TISSUES, INCLUDING LUNG, HEART, TESTIS, THYMUS, SPLEEN, EPIDIDYMAL FAT, HIPPOCAMPUS, KIDNEY, LIVE, AFTER SHORT AND LONG TERM PM(2.5) EXPOSURE. AFTER ACUTE PM(2.5) EXPOSURE, THE GLOBAL HYPO-METHYLATION IN DNA WAS OBSERVED IN LUNG AND HEART. NOTABLY, AFTER CHRONIC PM(2.5) EXPOSURE, LEVEL OF GLOBAL DNA METHYLATION DECREASED IN MOST ORGANS WHICH INCLUDED LUNG, TESTIS, THYMUS, SPLEEN, EPIDIDYMAL FAT, HIPPOCAMPUS AND BLOOD. THE PRESENT STUDY SYSTEMATICALLY DEMONSTRATED THE GLOBAL DNA METHYLATION CHANGES BY PM(2.5) EXPOSURE, AND PUT FORWARD A POSSIBLE ORIENTATION FOR FURTHER EXPLORING THE EFFECTS OF AMBIENT AIR PARTICLES EXPOSURE ON THE SPECIFIC ORGANS. 2019 13 2278 32 EPIGENETIC REGULATION BY SUV4-20H1 IN CARDIOPULMONARY PROGENITOR CELLS IS REQUIRED TO PREVENT PULMONARY HYPERTENSION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. BACKGROUND: THE PATHOGENESIS OF LIFE-THREATENING CARDIOPULMONARY DISEASES SUCH AS PULMONARY HYPERTENSION (PH) AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) ORIGINATES FROM A COMPLEX INTERPLAY OF ENVIRONMENTAL FACTORS AND GENETIC PREDISPOSITIONS THAT IS NOT FULLY UNDERSTOOD. LIKEWISE, LITTLE IS KNOWN ABOUT DEVELOPMENTAL ABNORMALITIES OR EPIGENETIC DYSREGULATIONS THAT MIGHT PREDISPOSE FOR PH OR COPD IN ADULT INDIVIDUALS. METHODS: TO IDENTIFY PATHOLOGY-ASSOCIATED EPIGENETIC ALTERATION IN DISEASED LUNG TISSUES, WE SCREENED A COHORT OF HUMAN PATIENTS WITH PH AND COPD FOR CHANGES OF HISTONE MODIFICATIONS BY IMMUNOFLUORESCENCE STAINING. TO ANALYZE THE FUNCTION OF H4K20ME2/3 IN LUNG PATHOGENESIS, WE DEVELOPED A SERIES OF SUV4-20H1 KNOCKOUT MOUSE LINES TARGETING CARDIOPULMONARY PROGENITOR CELLS AND DIFFERENT HEART AND LUNG CELL TYPES, FOLLOWED BY HEMODYNAMIC STUDIES AND MORPHOMETRIC ASSESSMENT OF TISSUE SAMPLES. MOLECULAR, CELLULAR, AND BIOCHEMICAL TECHNIQUES WERE APPLIED TO ANALYZE THE FUNCTION OF SUV4-20H1-DEPENDENT EPIGENETIC PROCESSES IN CARDIOPULMONARY PROGENITOR CELLS AND THEIR DERIVATIVES. RESULTS: WE DISCOVERED A STRONG REDUCTION OF THE HISTONE MODIFICATIONS OF H4K20ME2/3 IN HUMAN PATIENTS WITH COPD BUT NOT PATIENTS WITH PH THAT DEPEND ON THE ACTIVITY OF THE H4K20 DI-METHYLTRANSFERASE SUV4-20H1. LOSS OF SUV4-20H1 IN CARDIOPULMONARY PROGENITOR CELLS CAUSED A COPD-LIKE/PH PHENOTYPE IN MICE INCLUDING THE FORMATION OF PERIVASCULAR TERTIARY LYMPHOID TISSUE AND GOBLET CELL HYPERPLASIA, HYPERPROLIFERATION OF SMOOTH MUSCLE CELLS/MYOFIBROBLASTS, IMPAIRED ALVEOLARIZATION AND MATURATION DEFECTS OF THE MICROVASCULATURE LEADING TO MASSIVE RIGHT VENTRICULAR DILATATION AND PREMATURE DEATH. MECHANISTICALLY, SUV4-20H1 BINDS DIRECTLY TO THE 5'-UPSTREAM REGULATORY ELEMENT OF THE SUPEROXIDE DISMUTASE 3 (SOD3) GENE TO REPRESS ITS EXPRESSION. INCREASED LEVELS OF THE EXTRACELLULAR SOD3 ENZYME IN SUV4-20H1 MUTANTS INCREASES HYDROGEN PEROXIDE CONCENTRATIONS, CAUSING VASCULAR DEFECTS AND IMPAIRING ALVEOLARIZATION. CONCLUSIONS: OUR FINDINGS REVEAL A PIVOTAL ROLE OF THE HISTONE MODIFIER SUV4-20H1 IN CARDIOPULMONARY CODEVELOPMENT AND UNCOVER THE DEVELOPMENTAL ORIGINS OF CARDIOPULMONARY DISEASES. WE ASSUME THAT THE STUDY WILL FACILITATE THE UNDERSTANDING OF PATHOGENIC EVENTS CAUSING PH AND COPD AND AID THE DEVELOPMENT OF EPIGENETIC DRUGS FOR THE TREATMENT OF CARDIOPULMONARY DISEASES. 2021 14 5179 31 PREGNANCY: AN UNDERUTILIZED WINDOW OF OPPORTUNITY TO IMPROVE LONG-TERM MATERNAL AND INFANT HEALTH-AN APPEAL FOR CONTINUOUS FAMILY CARE AND INTERDISCIPLINARY COMMUNICATION. PHYSIOLOGIC ADAPTATIONS DURING PREGNANCY UNMASK A WOMAN'S PREDISPOSITION TO DISEASES. COMPLICATIONS ARE INCREASINGLY PREDICTED BY FIRST-TRIMESTER ALGORITHMS, AMPLIFY A PRE-EXISTING MATERNAL PHENOTYPE AND ACCELERATE RISKS FOR CHRONIC DISEASES IN THE OFFSPRING UP TO ADULTHOOD (BARKER HYPOTHESIS). RECENT EVIDENCE SUGGESTS THAT VICE VERSA, PREGNANCY DISEASES ALSO INDICATE MATERNAL AND EVEN GRANDPARENT'S RISKS FOR CHRONIC DISEASES (REVERSE BARKER HYPOTHESIS). PUB-MED AND EMBASE WERE REVIEWED FOR MESH TERMS "FETAL PROGRAMMING" AND "PREGNANCY COMPLICATIONS COMBINED WITH MATERNAL DISEASE" UNTIL JANUARY 2017. STUDIES LINKING PREGNANCY COMPLICATIONS TO FUTURE CARDIOVASCULAR, METABOLIC, AND THROMBOTIC RISKS FOR MOTHER AND OFFSPRING WERE REVIEWED. WOMEN WITH A HISTORY OF MISCARRIAGE, FETAL GROWTH RESTRICTION, PREECLAMPSIA, PRETERM DELIVERY, OBESITY, EXCESSIVE GESTATIONAL WEIGHT GAIN, GESTATIONAL DIABETES, SUBFERTILITY, AND THROMBOPHILIA MORE FREQUENTLY DEMONSTRATE WITH ECHOCARDIOGRAPHIC ABNORMALITIES, HIGHER FASTING INSULIN, DEVIATING LIPIDS OR CLOTTING FACTORS AND SHOW DEFECTIVE ENDOTHELIAL FUNCTION. THROMBOPHILIA HINTS TO THROMBOTIC RISKS IN LATER LIFE. PREGNANCY ABNORMALITIES CORRELATE WITH FUTURE CARDIOVASCULAR AND METABOLIC COMPLICATIONS AND EARLIER MORTALITY. CONVERSELY, WOMEN WITH A NORMAL PREGNANCY HAVE LOWER RATES OF SUBSEQUENT DISEASES THAN THE GENERAL FEMALE POPULATION CREATING THE TERM: "PREGNANCY AS A WINDOW FOR FUTURE HEALTH." ALTHOUGH THE PLACENTA WORKS AS A GATEKEEPER, MANY PREGNANCY COMPLICATIONS MAY LEAD TO SICKNESS AND EARLIER DEATH IN LATER LIFE WHEN THE CHILD BECOMES AN ADULT. THE EPIGENETIC MECHANISMS AND THE MISMATCH BETWEEN PRE- AND POSTNATAL LIFE HAVE CREATED THE TERM "FETAL ORIGIN OF ADULT DISEASE." UP TO NOW, THE IMPACT OF CARDIOVASCULAR, METABOLIC, OR THROMBOTIC RISK PROFILES HAS BEEN INVESTIGATED SEPARATELY FOR MOTHER AND CHILD. IN THIS MANUSCRIPT, WE STRIVE TO ILLUSTRATE THE CONSEQUENCES FOR BOTH, FETUS AND MOTHER WITHIN A COHESIVE PERSPECTIVE AND THUS TRY TO DEMONSTRATE THE COMPLEX INTERRELATIONSHIP OF GENETICS AND EPIGENETICS FOR LONG-TERM HEALTH OF SOCIETIES AND FUTURE GENERATIONS. MATERNAL-FETAL MEDICINE SPECIALISTS SHOULD HAVE A KEY ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES BY IMPLEMENTING A FRAMEWORK FOR PATIENT CONSULTATION AND INTERDISCIPLINARY NETWORKS. HEALTH-CARE PROVIDERS AND POLICY MAKERS SHOULD INCREASINGLY INVEST IN A STRATIFIED PRIMARY PREVENTION AND FOLLOW-UP TO REDUCE THE INCREASING NUMBER OF MANIFEST CARDIOVASCULAR AND METABOLIC DISEASES AND TO PREVENT WASTE OF HEALTH-CARE RESOURCES. 2017 15 4066 20 MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION AS AN INDICATOR OF OFFSPRING METABOLIC SYNDROME RISK IN LATER LIFE THROUGH EPIGENETIC IMPRINTING: A SYSTEMATIC REVIEW. AIMS: THIS REVIEW EXAMINED WHETHER MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION EFFECTS AN OFFSPRING'S LIKELIHOOD OF DEVELOPING CHRONIC METABOLIC RELATED CONDITIONS DUE TO EPIGENETIC IMPRINTING. METHODS: A LITERATURE SEARCH WAS CONDUCTED IN MULTIPLE SCIENCE DATABASES AND LIMITED TO STUDIES PUBLISHED AFTER 2012, IN ENGLISH LANGUAGE AND PEER REVIEWED. THE DATA FROM SELECTED ARTICLES WERE EXTRACTED AND A QUALITATIVE APPROACH WAS EMPLOYED DUE TO HETEROGENEITY OF RESULTS. RESULTS: NEWBORNS FROM OBESE FATHERS SHOWED ALTERED METHYLATION OVERALL AND SIGNIFICANT HYPOMETHYLATION AT THE INSULIN-LIKE GROWTH FACTOR 2 (IGF2) GENE. HIGH MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) WAS ASSOCIATED WITH ALTERED OFFSPRING DNA METHYLATION LEVELS AND GESTATIONAL DIABETES MELLITUS INDUCED SIGNIFICANTLY INCREASED METHYLATION LEVELS IN OFFSPRING. GESTATIONAL WEIGHT GAIN WAS NOT ASSOCIATED WITH DIFFERENTIALLY METHYLATED CORD BLOOD. BIRTH WEIGHT WAS HIGHER IN OFFSPRING EXPOSED TO FAMINE IN EARLY GESTATION. OFFSPRING BORN POST MATERNAL BARIATRIC SURGERY SHOWED A LOWER PERCENTAGE OF BODY FAT AND IMPROVED FASTING INSULIN LEVELS COMPARED TO SIBLINGS BORN PRE-MATERNAL BARIATRIC SURGERY. CONCLUSIONS: THE AVAILABLE EVIDENCE SUGGESTS THAT POOR MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION CAN INCREASE THE RISK OF METABOLIC SYNDROME IN OFFSPRING, THROUGH EPIGENETIC IMPRINTING. POTENTIAL PARENTS SHOULD BE ADVISED THAT MAINTAINING A HEALTHY DIET AND BMI IS LIKELY TO REDUCE THE RISK OF METABOLIC SYNDROME IN OFFSPRING. 2017 16 2605 18 EPIGENETICS-A POTENTIAL MEDIATOR BETWEEN AIR POLLUTION AND PRETERM BIRTH. PRETERM BIRTH IS A MAJOR CAUSE OF INFANT MORBIDITY AND MORTALITY AND A POTENTIAL RISK FACTOR FOR ADULT CHRONIC DISEASE. WITH OVER 15 MILLION INFANTS BORN PRETERM WORLDWIDE EACH YEAR, PRETERM BIRTH POSES A GLOBAL HEALTH CONCERN. THERE IS A POSSIBLE ASSOCIATION BETWEEN AIR POLLUTION AND PRETERM BIRTH, THOUGH STUDIES HAVE BEEN INCONSISTENT, LIKELY DUE TO VARIATION IN STUDY DESIGN. HOW AIR POLLUTION INDUCES HEALTH EFFECTS IS UNCERTAIN; HOWEVER, STUDIES HAVE REPEATEDLY DEMONSTRATED THE EFFECTS OF AIR POLLUTION ON EPIGENETIC MODIFICATIONS. MORE RECENT EVIDENCE SUGGESTS THAT EPIGENETICS MAY, IN TURN, BE LINKED TO PRETERM BIRTH. DISCOVERY OF ENVIRONMENTALLY MODIFIABLE EPIGENETIC PROCESSES CONNECTED TO PRETERM BIRTH MAY HELP TO IDENTIFY WOMEN AT RISK OF PRETERM BIRTH, AND ULTIMATELY LEAD TO DEVELOPMENT OF NEW PRETERM BIRTH PREVENTION MEASURES. 2016 17 4109 27 MECHANISMS AND DRUG THERAPY OF PULMONARY HYPERTENSION AT HIGH ALTITUDE. PULMONARY VASOCONSTRICTION REPRESENTS A PHYSIOLOGICAL ADAPTIVE MECHANISM TO HIGH ALTITUDE. IF EXAGGERATED, HOWEVER, IT IS ASSOCIATED WITH IMPORTANT MORBIDITY AND MORTALITY. RECENT MECHANISTIC STUDIES USING SHORT-TERM ACUTE HIGH ALTITUDE EXPOSURE HAVE PROVIDED INSIGHT INTO THE IMPORTANCE OF DEFECTIVE VASCULAR ENDOTHELIAL AND RESPIRATORY EPITHELIAL NITRIC OXIDE (NO) SYNTHESIS, INCREASED ENDOTHELIN-1 BIOAVAILABILITY, AND OVERACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM IN CAUSING EXAGGERATED HYPOXIC PULMONARY HYPERTENSION IN HUMANS. BASED ON THESE STUDIES, DRUGS THAT INCREASE NO BIOAVAILABILITY, ATTENUATE ENDOTHELIN-1 INDUCED PULMONARY VASOCONSTRICTION, OR PREVENT EXAGGERATED SYMPATHETIC ACTIVATION HAVE BEEN SHOWN TO BE USEFUL FOR THE TREATMENT/PREVENTION OF EXAGGERATED PULMONARY HYPERTENSION DURING ACUTE SHORT-TERM HIGH ALTITUDE EXPOSURE. THE MECHANISMS UNDERPINNING CHRONIC PULMONARY HYPERTENSION IN HIGH ALTITUDE DWELLERS ARE LESS WELL UNDERSTOOD, BUT RECENT EVIDENCE SUGGESTS THAT THEY DIFFER IN SOME ASPECTS FROM THOSE INVOLVED IN SHORT-TERM ADAPTATION TO HIGH ALTITUDE. THESE DIFFERENCES HAVE CONSEQUENCES FOR THE CHOICE OF THE TREATMENT FOR CHRONIC PULMONARY HYPERTENSION AT HIGH ALTITUDE. FINALLY, RECENT DATA INDICATE THAT FETAL PROGRAMMING OF PULMONARY VASCULAR DYSFUNCTION IN OFFSPRING OF PREECLAMPSIA AND CHILDREN GENERATED BY ASSISTED REPRODUCTIVE TECHNOLOGIES REPRESENTS A NOVEL AND FREQUENT CAUSE OF PULMONARY HYPERTENSION AT HIGH ALTITUDE. IN ANIMAL MODELS OF FETAL PROGRAMMING OF HYPOXIC PULMONARY HYPERTENSION, EPIGENETIC MECHANISMS PLAY A ROLE, AND TARGETING OF THESE MECHANISMS WITH DRUGS LOWERS PULMONARY ARTERY PRESSURE. IF EPIGENETIC MECHANISMS ALSO ARE OPERATIONAL IN THE FETAL PROGRAMMING OF PULMONARY VASCULAR DYSFUNCTION IN HUMANS, SUCH DRUGS MAY BECOME NOVEL TOOLS FOR THE TREATMENT OF HYPOXIC PULMONARY HYPERTENSION. 2013 18 246 27 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 19 649 30 BIRTHWEIGHT, MATERNAL WEIGHT TRAJECTORIES AND GLOBAL DNA METHYLATION OF LINE-1 REPETITIVE ELEMENTS. LOW BIRTHWEIGHT, PREMATURE BIRTH, INTRAUTERINE GROWTH RETARDATION, AND MATERNAL MALNUTRITION HAVE BEEN RELATED TO AN INCREASED RISK OF CARDIOVASCULAR DISEASE, TYPE 2 DIABETES MELLITUS, OBESITY, AND NEUROPSYCHIATRIC DISORDERS LATER IN LIFE. CONVERSELY, HIGH BIRTHWEIGHT HAS BEEN LINKED TO FUTURE RISK OF CANCER. GLOBAL DNA METHYLATION ESTIMATED BY THE METHYLATION OF REPETITIVE SEQUENCES IN THE GENOME IS AN INDICATOR OF SUSCEPTIBILITY TO CHRONIC DISEASES. WE USED DATA AND BIOSPECIMENS FROM AN EPIGENETIC BIRTH COHORT TO EXPLORE THE ASSOCIATION BETWEEN TRAJECTORIES OF FETAL AND MATERNAL WEIGHT AND LINE-1 METHYLATION IN 319 MOTHER-CHILD DYADS. NEWBORNS WITH LOW OR HIGH BIRTHWEIGHT HAD SIGNIFICANTLY LOWER LINE-1 METHYLATION LEVELS IN THEIR CORD BLOOD COMPARED TO NORMAL WEIGHT INFANTS AFTER ADJUSTING FOR GESTATIONAL AGE, SEX OF THE CHILD, MATERNAL AGE AT DELIVERY, AND MATERNAL SMOKING DURING PREGNANCY (P = 0.007 AND P = 0.036, RESPECTIVELY), BUT THE MAGNITUDE OF THE DIFFERENCE WAS SMALL. INFANTS BORN PREMATURELY ALSO HAD LOWER LINE-1 METHYLATION LEVELS IN CORD BLOOD COMPARED TO TERM INFANTS, AND THIS DIFFERENCE, THOUGH SMALL, WAS STATISTICALLY SIGNIFICANT (P = 0.004). WE DID NOT FIND IMPORTANT ASSOCIATIONS BETWEEN MATERNAL PREPREGNANCY BMI OR GESTATIONAL WEIGHT GAIN AND GLOBAL METHYLATION OF THE CORD BLOOD OR FETAL PLACENTAL TISSUE. IN CONCLUSION, WE FOUND SIGNIFICANT DIFFERENCES IN CORD BLOOD LINE-1 METHYLATION AMONG NEWBORNS WITH LOW AND HIGH BIRTHWEIGHT AS WELL AS AMONG PREMATURELY BORN INFANTS. FUTURE STUDIES MAY ELUCIDATE WHETHER CHROMOSOMAL INSTABILITIES OR OTHER FUNCTIONAL CONSEQUENCES OF THESE CHANGES CONTRIBUTE TO THE INCREASED RISK OF CHRONIC DISEASES AMONG INDIVIDUALS WITH THESE CHARACTERISTICS. 2011 20 298 29 AIR POLLUTION AND AIRWAY DISEASE. EPIDEMIOLOGICAL AND TOXICOLOGICAL RESEARCH CONTINUES TO SUPPORT A LINK BETWEEN URBAN AIR POLLUTION AND AN INCREASED INCIDENCE AND/OR SEVERITY OF AIRWAY DISEASE. DETRIMENTAL EFFECTS OF OZONE (O(3)), NITROGEN DIOXIDE (NO(2)) AND PARTICULATE MATTER (PM), AS WELL AS TRAFFIC-RELATED POLLUTION AS A WHOLE, ON RESPIRATORY SYMPTOMS AND FUNCTION ARE WELL DOCUMENTED. NOT ONLY DO WE HAVE STRONG EPIDEMIOLOGICAL EVIDENCE OF A RELATIONSHIP BETWEEN AIR POLLUTION AND EXACERBATION OF ASTHMA AND RESPIRATORY MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), BUT RECENT STUDIES, PARTICULARLY IN URBAN AREAS, HAVE SUGGESTED A ROLE FOR POLLUTANTS IN THE DEVELOPMENT OF BOTH ASTHMA AND COPD. SIMILARLY, WHILE PREVALENCE AND SEVERITY OF ATOPIC CONDITIONS APPEAR TO BE MORE COMMON IN URBAN COMPARED WITH RURAL COMMUNITIES, EVIDENCE IS EMERGING THAT TRAFFIC-RELATED POLLUTANTS MAY CONTRIBUTE TO THE DEVELOPMENT OF ALLERGY. FURTHERMORE, NUMEROUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST AN ASSOCIATION BETWEEN EXPOSURE TO NO(2) , O(3) , PM AND COMBUSTION PRODUCTS OF BIOMASS FUELS AND AN INCREASED SUSCEPTIBILITY TO AND MORBIDITY FROM RESPIRATORY INFECTION. GIVEN THE CONSIDERABLE CONTRIBUTION THAT TRAFFIC EMISSIONS MAKE TO URBAN AIR POLLUTION RESEARCHERS HAVE SOUGHT TO CHARACTERIZE THE RELATIVE TOXICITY OF TRAFFIC-RELATED PM POLLUTANTS. RECENT ADVANCES IN MECHANISMS IMPLICATED IN THE ASSOCIATION OF AIR POLLUTANTS AND AIRWAY DISEASE INCLUDE EPIGENETIC ALTERATION OF GENES BY COMBUSTION-RELATED POLLUTANTS AND HOW POLYMORPHISMS IN GENES INVOLVED IN ANTIOXIDANT PATHWAYS AND AIRWAY INFLAMMATION CAN MODIFY RESPONSES TO AIR POLLUTION EXPOSURES. OTHER INTERESTING EPIDEMIOLOGICAL OBSERVATIONS RELATED TO INCREASED HOST SUSCEPTIBILITY INCLUDE A POSSIBLE LINK BETWEEN CHRONIC PM EXPOSURE DURING CHILDHOOD AND VULNERABILITY TO COPD IN ADULTHOOD, AND THAT INFANTS SUBJECTED TO HIGHER PRENATAL LEVELS OF AIR POLLUTION MAY BE AT GREATER RISK OF DEVELOPING RESPIRATORY CONDITIONS. WHILE THE CHARACTERIZATION OF POLLUTANT COMPONENTS AND SOURCES PROMISE TO GUIDE POLLUTION CONTROL STRATEGIES, THE IDENTIFICATION OF SUSCEPTIBLE SUBPOPULATIONS WILL BE NECESSARY IF TARGETED THERAPY/PREVENTION OF POLLUTION-INDUCED RESPIRATORY DISEASES IS TO BE DEVELOPED. 2011