A5023205717- Hormonal Regulation and Hypertension
- Cardiac Valve Diseases and Treatments
- Sodium Intake and Health
- Congenital heart defects research
- Atrial Fibrillation Management and Outcomes
- Cardiovascular Function and Risk Factors
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Congenital Heart Disease Studies
- Aortic Disease and Treatment Approaches
- Renin-Angiotensin System Studies
- Cardiac Imaging and Diagnostics
- T-cell and B-cell Immunology
- Nutrition, Genetics, and Disease
- Cancer-related molecular mechanisms research
- Cardiac Ischemia and Reperfusion
- Infective Endocarditis Diagnosis and Management
- Genetic and phenotypic traits in livestock
- Mitochondrial Function and Pathology
- Heart Rate Variability and Autonomic Control
- Sex and Gender in Healthcare
- Vitamin D Research Studies
- Cardiac electrophysiology and arrhythmias
- Circular RNAs in diseases
- Adipokines, Inflammation, and Metabolic Diseases
Brigham and Women's Hospital
2016-2025
Harvard University
2016-2025
Mass General Brigham
2024
King Chulalongkorn Memorial Hospital
2023
Thai Red Cross Society
2023
Chulalongkorn University
2023
University of Ottawa
2018
Sahyadri Hospital
2017
Abbott Northwestern Hospital
2015
Zero to Three
2015
Abstract Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy aortopathy. Here we report genome-wide association scan of 466 BAV cases 4,660 age, sex ethnicity-matched controls with replication in up to 1,326 8,103 controls. We identify noncoding variant 151 kb from the gene encoding cardiac-specific transcription factor, GATA4, near-significance p.Ser377Gly GATA4 . was interrupted by CRISPR-Cas9 induced pluripotent stem cells...
Bicuspid aortic valve (BAV), the most common congenital heart defect affecting 1% to 2% of population, is a major risk factor for premature disease and accounts majority replacement. The genetic basis mechanisms BAV etiology pathogenesis remain largely undefined.Cardiac structure function was assessed in mice lacking Gata6 allele. Human GATA6 gene variants were analyzed 452 cases from consortium 1849 controls Framingham GWAS (Genome Wide Association Study). expression determined human...
Importance Nonsyndromic bicuspid aortic valve (nsBAV) is the most common congenital heart malformation. BAV has a heritable component, yet only few causative genes have been identified; understanding genetics key point in developing personalized medicine. Objective To identify new gene for nsBAV. Design, Setting, and Participants This was comprehensive, multicenter, genetic association study based on candidate prioritization familial cohort followed by rare studies replication cohorts....
Background Adiponectin, a secretagogue exclusively produced by adipocytes, has been associated with metabolic features, but its role in the development of syndrome remains unclear. Objectives We investigated association between serum adiponectin level and traits, using both observational genetic epidemiologic approaches multiethnic population assembled Canada. Methods Clinical data were collected 1,157 participants SHARE/SHARE-AP studies. Participants genotyped for functional rs266729...
Bicuspid aortic valve (BAV) disease is a congenital defect that affects 0.5% to 1.2% of the population and associated with comorbidities including ascending dilation calcific stenosis. To date, although few causal genes have been identified, genetic basis for vast majority BAV cases remains unknown, likely pointing complex heterogeneity underlying this phenotype. Identifying pathways versus individual gene variants may provide an avenue uncovering additional causes consequent...
Summary The estimation of (co)variance components for multiple traits with maternal genetic effects was found to be influenced by population structure. Two in a closed breeding herd random mating were simulated over nine generations. Population structures on the basis different proportions dams not having performance records (0, 0.1, 0.5, 0.8 and 0.9): three correlations (−0.5, 0.0 +0.5) between direct 0.3 0.8) two traits. Three ratios variances, (1:3, 1:1, 3:1), also considered. Variance...
Introduction Propionic acid (PA) is a common food preservative generally recognized as safe by the US Food and Drug Administration; however, exogenous PA has effects on glucose metabolism that are not fully understood. Our preclinical studies demonstrated increases glucagon, norepinephrine, endogenous production (EGP). Research design methods We performed randomized, placebo-controlled, crossover study in 28 healthy men women to determine effect of (1500 mg calcium propionate) these factors....
MicroRNAs (miRNAs) play a significant role in ischemic heart disease. Animal models of left ventricular (LV) ischemia demonstrate unique miRNA profile; however, these have limitations describing human In this study, we performed next-generation and mRNA sequencing on LV tissue from nine patients undergoing cardiac surgery with cardiopulmonary bypass cardioplegic arrest. Samples were obtained immediately after aortic cross clamping (baseline) before clamp removal (postischemic). Of 1,237...
Sex differences exist in the prevalence, presentation and outcomes of ischemic heart disease (IHD). Females have higher risk failure post-myocardial infarction relative to males are two three times more likely die after coronary artery bypass grafting surgery. We examined sex human myocardial gene expression response ischemia. Left ventricular biopsies from 68 male/46 female patients undergoing aortic valve replacement surgery were obtained at baseline a median 74 min cold cardioplegic...
The exact mechanisms that underlie the pathological processes of myocardial ischemia in humans are unclear. Cardiopulmonary bypass with cardioplegic arrest allows authors to examine whole transcriptional profile human left ventricular myocardium at baseline and after exposure cold cardioplegia-induced as a model.
Abstract Background Our goal was to determine in healthy individuals and with type 2 diabetes the impact of repeated episodes hypoglycemia on corrected QT (QTc) interval time course for QTc recovery. Further, since increases aldosterone patients primary aldosteronism have prolonged QTc, we also determined whether mineralocorticoid receptor blockade prevents hypoglycemia-induced alterations. Methods Twenty-seven participants completed a double-blinded crossover trial contrasting 3...
Risk alleles in lysine specific demethylase 1 (LSD1) and striatin (STRN) are independently associated with greater salt sensitive blood pressure (SSBP) increased aldosterone and/or mineralocorticoid receptor (MR) activity. We tested the hypothesis that Black, but not White, risk allele carriers both genes would have a more severe degree of SSBP than those carrying single from either gene alone. Individuals HyperPATH cohort were assessed for hormone levels after controlled low liberal sodium...
Abstract Background High dietary sodium intake is associated with cardiovascular disease. We investigated the influence of on plasma proteome. Methods Prospectively recruited normotensive participants underwent 2 controlled interventions to evaluate hormonal and proteomic (1,512 proteins) changes: sodium-restriction resembling ancestral hunter-gatherer (~10 mEq/day, ~230mg/day) sodium-loading modern industrialized (~200 ~4600mg/day). 24h urine collections were obtained after each diet....
Background— Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection subjects who both experience and survive the primary indexing event. Currently, magnitude any bias, particularly for time-to-event analysis in genetic association studies, is unknown. Methods Results— We used empirically inspired simulation studies explore impact on marginal hazard ratio risk among those with established coronary heart disease. The extent was determined magnitudes...
Background— The discovery of functional classes long noncoding RNAs (lncRNAs) has expanded our understanding the variety RNA species that exist in cells. In heart, lncRNAs have been implicated regulation development, ischemic and dilated cardiomyopathy, myocardial infarction. Nevertheless, there is a limited description expression profiles for these transcripts human subjects. Methods Results— We obtained left ventricular tissue from patients undergoing cardiac surgery used sequencing to...
Both ambulatory atrial fibrillation (AF) and post-operative AF (poAF) are associated with substantial morbidity mortality. Analyzing the tissue-specific gene expression in left atrium (LA) can identify novel genes further understanding of mechanism by which previously identified genetic variants mediate their effects. LA free wall samples were obtained intraoperatively immediately prior to mitral valve surgery 62 Caucasian individuals. Gene was quantified on mRNA harvested from these using...
Operating rooms (ORs) are an important source of hospital revenue, and utilization rate is a key determinant OR efficiency. Multiple factors contribute to underutilization, managers may have biased views about which most underutilization. We examined various leading underutilization at one academic tertriary care center.Data were collected retrospectively from over 12-month period. Contribution was measured in terms hours Statistical significance between categories days calculated using...
Background and Objectives: Regional anesthesia has been proposed as the preferred mode of for arteriovenous fistula surgery due to its associated vasodilatory effects patency rates. We analyzed patient outcomes after their association with type received. Methods: The National Surgical Quality Improvement Project database was accessed identify a cohort 3199 patients undergoing from 2007 2015. Multiple regression models were used examine 12 postoperative outcomes. Additional multivariate...
Salt sensitivity of blood pressure (SSBP) is associated with increased cardiovascular risk, especially in individuals African descent, although the underlying mechanisms remain obscure. Lysine-specific demethylase 1 (LSD1) a salt-sensitive epigenetic regulator SSBP and aldosterone dysfunction. An LSD1 risk allele humans lower levels hypertensive but not European descent. Heterozygous knockout mice display dysregulation, this effect modified by age biological sex. This might explain...