A5051535283- Cardiomyopathy and Myosin Studies
- Pulmonary Hypertension Research and Treatments
- Cardiovascular Effects of Exercise
- Congenital heart defects research
- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Cardiovascular Function and Risk Factors
- Pancreatic function and diabetes
- Cardiac electrophysiology and arrhythmias
- Viral Infections and Immunology Research
- RNA Research and Splicing
- Muscle Physiology and Disorders
- Cardiac pacing and defibrillation studies
- Sports injuries and prevention
- Neonatal Respiratory Health Research
- RNA modifications and cancer
- Transplantation: Methods and Outcomes
- Protease and Inhibitor Mechanisms
- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- Genetics and Neurodevelopmental Disorders
- COVID-19 Clinical Research Studies
- Vanadium and Halogenation Chemistry
- Vascular Anomalies and Treatments
- Global Health Workforce Issues
Sequoia (United States)
2024
SEQUOIA (Italy)
2024
University of Iowa
2014-2024
Oregon Health & Science University
2024
University of Pittsburgh
2007-2019
University of Iowa Hospitals and Clinics
2019
University of Pittsburgh Medical Center
2011-2013
Cardiovascular Institute Hospital
2010
Harvard University
2003-2009
Brigham and Women's Hospital
2003-2009
The Wolff-Parkinson-White syndrome, with a prevalence in Western countries of 1.5 to 3.1 per 1000 persons, causes considerable morbidity and may cause sudden death. We identified two families which the syndrome segregated as an autosomal dominant disorder.We studied 70 members (57 Family 1 13 2). subjects underwent 12-lead electrocardiography two-dimensional echocardiography. Genotyping mapped gene responsible 7q34-q36, locus previously be for inherited form syndrome. Candidate genes were...
Molecular etiologies of heart failure, an emerging cardiovascular epidemic affecting 4.7 million Americans and costing 17.8 billion health-care dollars annually, remain poorly understood. Here we report that inherited human dilated cardiomyopathy with refractory congestive failure is caused by a dominant Arg → Cys missense mutation at residue 9 (R9C) in phospholamban (PLN), transmembrane phosphoprotein inhibits the cardiac sarcoplasmic reticular Ca 2+ –adenosine triphosphatase (SERCA2a)...
Importance Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias individuals hypertrophic cardiomyopathy (HCM) unknown. Objective To determine whether engagement increased for and/or mortality HCM. The a priori hypothesis was that participants engaging activity were not more likely to have arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants This investigator-initiated, prospective cohort...
Mutations in the gamma2 subunit (PRKAG2) of AMP-activated protein kinase produce an unusual human cardiomyopathy characterized by ventricular hypertrophy and electrophysiological abnormalities: Wolff-Parkinson-White syndrome (WPW) progressive degenerative conduction system disease. Pathological examinations affected hearts reveal vacuoles containing amylopectin, a glycogen-related substance.To elucidate mechanism which PRKAG2 mutations with abnormalities, we constructed transgenic mice...
Cardiac myocytes depend on a delicate balance of glucose and free fatty acids as energy sources, that is disrupted in pathological states such diabetic cardiomyopathy myocardial ischaemia. There are two families cellular transporters: the facilitated-diffusion transporters (GLUT); sodium-dependent (SGLT). It has long been thought only GLUT isoforms, GLUT1 GLUT4, responsible for cardiac myocyte uptake. However, we discovered one SGLT isoform, SGLT1, also an important transporter heart. In...
Background —Arrhythmogenic right ventricular dysplasia (ARVD), a familial cardiomyopathy occurring with prevalence of 1 in 5000, is characterized by replacement myocytes fatty and fibrous tissue. Clinical manifestations include structural functional abnormalities the ventricle arrhythmias, leading to sudden death rate 2.5% per year. Four loci have been mapped, but no gene has identified as yet. Methods Results —We large family >200 members ARVD segregating an autosomal dominant trait...
Idiopathic pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by arteriolar remodeling. This investigation aimed to identify genes involved specifically in the pathogenesis of PAH and not other forms (PH). Using genomewide microarray analysis, we generated largest data set date RNA expression profiles from lung tissue specimens 1) 18 subjects 2) 8 with PH secondary idiopathic fibrosis (IPF) 3) 13 normal subjects. A molecular signature 4,734 discriminated...
Cardiovascular genetics is a rapidly evolving subspecialty within cardiovascular medicine, and its growth attributed to advances in genome sequencing genetic testing the expanding understanding of basis multiple cardiac conditions, including arrhythmias (channelopathies), heart failure (cardiomyopathies), lipid disorders, complications neuromuscular vascular disease, aortopathies. There have also been great clinical diagnostic methods, as well therapies ameliorate symptoms, slow progression...
Abstract Background Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital disease, others) but often the etiology idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 ( BMPR2 ) are cause most heritable cases vast majority genetically...
Survival rates for patients with pulmonary hypertension (PH) remain low, and our understanding of the mechanisms involved are incomplete. Here we show in a mouse model chronic hypoxia (CH)-induced PH that nuclear protein damage-associate molecular pattern molecule (DAMP) high mobility group box 1 (HMGB1) contributes to via Toll-like receptor 4 (TLR4)-dependent mechanism. We demonstrate extranuclear HMGB1 vascular lesions increased serum idiopathic arterial hypertension. The increase...
The expression of a novel cardiac glucose transporter, SGLT1, is increased in glycogen storage cardiomyopathy secondary to mutations PRKAG2. We sought determine the role SGLT1 pathogenesis PRKAG2 and its structure function.Transgenic mice with cardiomyocyte-specific overexpression human T400N mutant cDNA (TG(T400N)) transgenic RNA interference knockdown (TG(SGLT1-DOWN)) were crossed produce double-transgenic (TG(T400N)/TG(SGLT1-DOWN)). Tet-off conditionally overexpressing absence doxycycline...
We previously reported that sodium-dependent glucose cotransporter 1 (SGLT1) is highly expressed in cardiomyocytes and further up-regulated ischaemia. This study aimed to determine the mechanisms by which SGLT1 contributes ischaemia/reperfusion (I/R) injury.Mice with cardiomyocyte-specific knockdown of (TGSGLT1-DOWN) wild-type controls were studied. In vivo, left anterior descending coronary artery was ligated for 30 min reperfused 48 h. Ex isolated perfused hearts exposed 20 no-flow up 2 h...
Rationale: Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation circulating proteins. Objectives: To quantify analyze the plasma proteome patients with PAH using inherited genetic variation to inform on underlying molecular drivers. Methods: An aptamer-based assay was used measure proteins 357 idiopathic or heritable PAH, 103 healthy volunteers, 23 relatives...
Cardiac antigen-specific CD8(+) T cells are involved in the autoimmune component of human myocarditis. Here, we studied differentiation and migration pathogenic cell effector a new mouse model A transgenic line was derived that expresses cardiac myocyte restricted membrane-bound ovalbumin (CMy-mOva). The endogenous adaptive immune system CMy-mOva mice displays tolerance to ovalbumin. Adoptive transfer naive from ovalbumin-specific receptor-transgenic (TCR-transgenic) OT-I strain induces...
Dilated cardiomyopathy (DCM) leads to heart failure, a leading cause of death in industrialized nations. Approximately 30% DCM cases are genetic origin, with some resulting from point mutations cardiac myosin, the molecular motor heart. The effects these on myosin's mechanics have not been determined. We engineered two murine models characterizing physiological, cellular, and DCM-causing missense (S532P F764L) alpha-cardiac myosin heavy chain compared them WT mice. Mutant mice developed...
AMP-activated protein kinase (AMPK) regulatory gamma2 subunit (PRKAG2) mutations cause a human cardiomyopathy with cardiac hypertrophy, preexcitation, and glycogen deposition. PRKAG2 is recapitulated in transgenic mice overexpressing mutant N488I the heart (TGgamma2N488I). AMPK heterotrimeric consisting of 1 catalytic (alpha) 2 (beta gamma) subunits. Two alpha-subunit isoforms, alpha1 alpha2, are expressed heart; however, contribution utilization these subunits to unknown. Mice...
Background— PRKAG2 mutations cause glycogen-storage cardiomyopathy, ventricular preexcitation, and conduction system degeneration. A genetic approach that utilizes a binary inducible transgenic was used to investigate the disease mechanism assess preventability reversibility of features in mouse model cardiomyopathy. Methods Results— Transgenic (Tg) mice expressing human N488I cDNA under control tetracycline-repressible α-myosin heavy chain promoter underwent echocardiography, ECG, vivo...
Sex plays an important role in the clinical expression and prognosis of various cardiovascular diseases. This study was designed to observe effects sex on hypertrophic cardiomyopathy (HCM).A total 621 unrelated patients with HCM without heart failure (460 males) were enrolled from 1999 2011. Compared male patients, at baseline female older diagnosis (49.6±17.2 years vs. 46.7±14.4 years, P = 0.033), had greater frequency left ventricular outflow tract obstruction (72/161, 44.7% 149/460,...