A5061025856- Pulmonary Hypertension Research and Treatments
- Cardiovascular Function and Risk Factors
- Nitric Oxide and Endothelin Effects
- Hormonal Regulation and Hypertension
- Coronary Interventions and Diagnostics
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Cardiovascular Issues in Pregnancy
- Eicosanoids and Hypertension Pharmacology
- Heart Failure Treatment and Management
- Neonatal Health and Biochemistry
- Congenital Heart Disease Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiac Imaging and Diagnostics
- Acute Myocardial Infarction Research
- Vascular Anomalies and Treatments
- Cardiovascular Health and Risk Factors
- Cardiovascular Health and Disease Prevention
- Renin-Angiotensin System Studies
- Blood Pressure and Hypertension Studies
- Parathyroid Disorders and Treatments
- Cardiac Valve Diseases and Treatments
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Atherosclerosis and Cardiovascular Diseases
- Atrial Fibrillation Management and Outcomes
Brigham and Women's Hospital
2016-2025
Harvard University
2016-2025
National Institutes of Health
2024
National Heart Lung and Blood Institute
2024
Intermountain Medical Center
2023
VA Boston Healthcare System
2012-2021
Poznań University of Technology
2019
Boston Children's Hospital
2014-2018
Universidade Federal de São Paulo
2018
Medical University of Graz
2018
Background— Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, relevance of <25 Hg to clinical outcome unknown. Methods and Results— We analyzed retrospectively all US veterans undergoing right heart catheterization (2007–2012) in...
Homocysteine is a risk factor for the development of atherosclerosis and its thrombotic complications. We have employed an animal model to explore hypothesis that increase in reactive oxygen species subsequent loss nitric oxide bioactivity contribute endothelial dysfunction mild hyperhomocysteinemia. examined function vivo oxidant burden mice heterozygous deletion cystathionine β-synthase (CBS) gene, by studying isolated, precontracted aortic rings mesenteric arterioles situ. CBS–/+...
Glucose-6-phosphate dehydrogenase (G6PD), the principal source of NADPH, serves as an antioxidant enzyme to modulate redox milieu and nitric oxide synthase activity. Deficient G6PD activity is associated with increased endothelial cell oxidant stress diminished bioavailable (NO.). Therefore, we examined whether overexpression would decrease reactive oxygen species accumulation increase NO. in cells.Adenoviral-mediated gene transfer expression, activity, NADPH levels bovine aortic cells...
Patients with type 2 diabetes lose β cells, but the underlying mechanisms are incompletely understood. Glucose-6-phosphate dehydrogenase (G6PD) is principal source of major intracellular reduc-tant, NADPH, which required by many enzymes, including enzymes antioxidant pathway. Previous work from our laboratory has shown that high glucose impairs G6PD activity in endothelial and kidney leads to decreased cell survival. Pancreatic cells highly sensitive increased ROS. This study aimed determine...
Reactive oxygen species (ROS)–mediated cell injury contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. Protection against ROS requires maintenance endogenous thiol pools, most importantly, reduced glutathione (GSH), by NADPH. In cardiomyocytes, GSH resides in two separate cellular compartments: mitochondria cytosol. Although mitochondrial is maintained largely transhydrogenase isocitrate dehydrogenase, mechanisms responsible for sustaining cytosolic...
Pulmonary arterial hypertension (PAH) is characterized, in part, by decreased endothelial nitric oxide (NO(·)) production and elevated levels of endothelin-1. Endothelin-1 known to stimulate synthase (eNOS) via the endothelin-B receptor (ET(B)), suggesting that this signaling pathway perturbed PAH. also stimulates adrenal aldosterone synthesis; systemic blood vessels, hyperaldosteronism induces vascular dysfunction increasing reactive oxygen species generation decreasing NO(·) levels. We...
Glutathione peroxidase-1 (GPx-1) is a selenocysteine-containing enzyme that plays major role in the reductive detoxification of peroxides cells. In permanently transfected cells with approximate 2-fold overexpression GPx-1, we found intracellular accumulation oxidants response to exogenous hydrogen peroxide was diminished, as epidermal growth factor receptor (EGFR)-mediated Akt activation or EGF stimulation. Knockdown GPx-1 augmented EGFR-mediated activation, whereas catalase decreased...
Background— Glutathione peroxidase-3 (GPx-3) is a selenocysteine-containing plasma protein that scavenges reactive oxygen species in the extracellular compartment. A deficiency of this enzyme has been associated with platelet-dependent thrombosis, and promoter haplotype reduced function stroke risk. Methods Results— We recently developed genetic mouse model to assess platelet thrombosis setting GPx-3 deficiency. The (−/−) mice showed an attenuated bleeding time enhanced aggregation response...
Vascular calcification resembles bone formation and involves vascular smooth muscle cell (SMC) transition to an osteoblast-like phenotype express Runx2, a master osteoblast transcription factor. One possible mechanism by which Runx2 protein expression is induced downregulation of inhibitory microRNAs (miR).Human coronary artery SMCs (CASMCs) treated with morphogenetic protein-2 (BMP-2; 100 ng/mL) demonstrated 1.7-fold (P<0.02) increase in at 24 hours. A miR microarray target prediction...
Background— Pulmonary arterial hypertension (PAH) is characterized by dysregulated proliferation of pulmonary artery smooth muscle cells leading to (mal)adaptive vascular remodeling. In the systemic circulation, injury associated with downregulation sarcoplasmic reticulum Ca 2+ -ATPase 2a (SERCA2a) and alterations in homeostasis that stimulate proliferation. We, therefore, hypothesized SERCA2a permissive for remodeling development PAH. Methods Results— expression was decreased significantly...