A5103129700- Pulmonary Hypertension Research and Treatments
- Neurological Disorders and Treatments
- Neonatal Respiratory Health Research
- Cardiac Structural Anomalies and Repair
- Mechanical Circulatory Support Devices
- Cerebrovascular and Carotid Artery Diseases
- Cardiac Arrest and Resuscitation
- Migraine and Headache Studies
- Respiratory Support and Mechanisms
- GDF15 and Related Biomarkers
- Vascular Anomalies and Treatments
- Cardiac Valve Diseases and Treatments
- S100 Proteins and Annexins
- Cerebrovascular and genetic disorders
- Clusterin in disease pathology
- Acute Ischemic Stroke Management
- TGF-β signaling in diseases
- Liver Disease and Transplantation
- Cancer-related molecular mechanisms research
- Renin-Angiotensin System Studies
- Cardiac tumors and thrombi
- MicroRNA in disease regulation
- Cardiovascular Effects of Exercise
- Organ Transplantation Techniques and Outcomes
- Liver physiology and pathology
Harvard University
2015-2022
Massachusetts General Hospital
2019-2022
Brigham and Women's Hospital
2014-2019
Rationale: Transforming growth factor-β (TGF-β) ligands signal via type I and II serine-threonine kinase receptors to regulate broad transcriptional programs. Excessive TGF-β–mediated signaling is implicated in the pathogenesis of pulmonary arterial hypertension, based part on ability inhibition activin-like (ALK) 4/5/7 recognizing TGF-β, activin, differentiation factor, nodal attenuate experimental hypertension (PH). These strategies do not delineate specific contribution TGF-β versus a...
Rationale: Recently, rare heterozygous mutations in GDF2 were identified patients with pulmonary arterial hypertension (PAH). encodes the circulating BMP (bone morphogenetic protein) type 9, which is a ligand for BMP2 receptor.Objectives: Here we determined functional impact of and characterized plasma BMP9 BMP10 levels idiopathic PAH.Methods: Missense mutant proteins expressed vitro on protein processing secretion, endothelial signaling, activity was assessed. Plasma assayed PAH variants...
Rationale: BMP9 (bone morphogenetic protein 9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations BMP9, its receptors, and downstream effectors have been reported heritable PAH.Objectives: To determine how an acquired deficiency of signaling might contribute to PAH.Methods: Plasma levels antagonist soluble endoglin were measured group 1 PAH, 2 3 (PH), patients severe liver disease without...
Pulmonary endothelial permeability contributes to the high-permeability pulmonary edema that characterizes acute respiratory distress syndrome. Circulating BMP9 (bone morphogenetic protein 9) is emerging as an important regulator of vascular homeostasis.
Portopulmonary hypertension (POPH) is a poorly understood complication of liver disease associated with significant morbidity and mortality. We sought to identify novel biomarkers POPH presence severity. performed prospective, multicenter, case-control study involving patients undergoing right heart catheterization. cases were defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg vascular resistance (PVR) >240 dynes˙s˙cm-5. Plasma samples collected from the systemic circulation,...
Dysregulation of microRNA-21 (miR-21) is independently associated with HIV infection, pulmonary arterial hypertension (PAH), and hepatitis C virus (HCV) infection. To assess the expression miR-21 in these overlapping comorbidities, we measured plasma without PAH then stratified by concomitant HCV MiR-21 was increased HIV-PAH versus uninfected subjects, but it did not differ between groups. HIV/HCV coinfection correlated even higher levels within HIV-infected population. These data reveal...
ABSTRACT Rationale Pulmonary endothelial permeability contributes to the high-permeability pulmonary edema that characterizes acute respiratory distress syndrome (ARDS), which carries a high mortality. Circulating bone morphogeneic protein 9 (BMP9) is emerging as an important regulator of vascular homeostasis. Objective To determine whether endogenous BMP9 plays role in preserving integrity, and loss occurs during lipopolysacharride (LPS)-induced lung inflammation permeability. Methods A...
Introduction: Excessive Transforming Growth Factor-β (TGF-β) signaling has been implicated in pulmonary arterial hypertension (PAH), based on activation of TGF-β effectors and transcriptional targets affected lungs the ability type I receptor (ALK5) inhibitors to improve experimental PAH. However, clinical use ALK5 limited by cardiovascular toxicity. Hypothesis: We tested whether or not selective blockade Differentiation Factor (GDF) ligands using a recombinant TGFβ II extracellular domain...
Background: Dysregulated bone morphogenetic protein (BMP) signaling is thought to contribute the pathogenesis of pulmonary arterial hypertension (PAH). BMP9 can be detected in circulation at physiologically active concentrations, and serve as a vascular endothelial quiescence factor. Aim: We hypothesized that circulating levels might associated with altered homeostasis, could help predict presence PAH or distinguish between distinct etiologies. Methods: Circulating BMP9, its biological...