A5081535211- Hormonal Regulation and Hypertension
- Blood Coagulation and Thrombosis Mechanisms
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Protease and Inhibitor Mechanisms
- Circadian rhythm and melatonin
- Cholesterol and Lipid Metabolism
- Liver Disease Diagnosis and Treatment
- Signaling Pathways in Disease
- Urticaria and Related Conditions
- COVID-19 Clinical Research Studies
- Inflammatory mediators and NSAID effects
- Acute Myocardial Infarction Research
- Vehicle Noise and Vibration Control
- Psychological and Temporal Perspectives Research
- Platelet Disorders and Treatments
- Noise Effects and Management
- Diet, Metabolism, and Disease
- Food Allergy and Anaphylaxis Research
- Cardiac Fibrosis and Remodeling
- Apelin-related biomedical research
- Schizophrenia research and treatment
- Mental Health and Psychiatry
- Ion Transport and Channel Regulation
- Neuropeptides and Animal Physiology
Tufts Medical Center
2018-2023
Tufts University
2018-2021
Sinai Hospital
2021
Hudson Institute of Medical Research
2015-2019
The University of Melbourne
2012-2019
Sorbonne Paris Cité
2012
Monash University
2012
Université Paris Cité
2012
Rhode Island Hospital
1940
Mineralocorticoid receptor (MR) activation promotes the development of cardiac fibrosis and heart failure. Clinical evidence demonstrates that MR antagonism is protective even when plasma aldosterone levels are not increased. We hypothesize in macrophages drives profibrotic phenotype elevated. The aim present study was to establish role macrophage signaling mediating tissue remodeling caused by nitric oxide (NO) deficiency, a mineralocorticoid-independent insult. Male wild-type (MRflox/flox)...
Because the role of mineralocorticoid receptors in specific cell types cardiac remodeling remains unknown, we have compared responses with deoxycorticosterone/salt cardiomyocyte receptor-null (MyoMRKO) and wild-type (WT) mice at 8 days weeks. No differences function between untreated WT MyoMRKO were found, whereas profibrotic markers reduced hearts baseline. At days, showed monocyte/macrophage recruitment equivalent to response but a suppression fibrosis WT. weeks, no...
1. Of 641 clinically diagnosed cases of schizophrenia, admitted to the Rhode Island State Hospital for Mental Diseases, between 1929 and 1934, followed 5 10 years, 27.5 per cent were found be at present in community, 53.5 mental hosiptals, 13.9 dead 5.1 no adequate follow-up information could obtained. 2. Adequate data available 608 patients; these 6.6 much improved, 15.3 63.5 unimproved 14.6 dead. 3. Classification on basis diagnostic subtype showed that 35 simple, 16.4 hebephrenic, 30...
Insulin resistance and poor glycemic control are key drivers of the development NAFLD have recently been shown to be associated with fibrosis progression in NASH. However, underlying mechanisms involving dysfunctional glucose metabolism relationship NAFLD/NASH remain poorly understood. We set out determine whether protease-activated receptor 2 (PAR2), a sensor extracellular inflammatory coagulation proteases, links NASH liver metabolism.Here, we demonstrate that hepatic expression PAR2...
Protease-activated receptor-1 (PAR1) is classically activated by thrombin and critical in controlling the balance of hemostasis thrombosis. More recently, it has been shown that noncanonical activation PAR1 matrix metalloprotease-1 (MMP1) contributes to arterial However, role long-term development atherosclerosis unknown, regardless protease agonist.We found plasma MMP1 was significantly correlated (R=0.33; P=0.0015) with coronary atherosclerotic burden as determined angiography 91 patients...
Increases in hepatic and plasma cholesterol occur patients with nonalcoholic fatty liver disease (NAFLD), although the reason for this is not well understood. We investigated whether Protease-Activated Receptor 2 (PAR2) plays a role lipid homeostasis NAFLD. Human biopsies (n = 108) were quantified PAR2 expression from NAFLD cases randomly selected stratified by fibrosis stage, primary predictor clinical outcomes, while controlling age, gender, BMI between groups. Demographic data laboratory...
Arterial thrombosis leading to ischemic injury worsens the prognosis of many patients with cardiovascular disease. PZ-128 is a first-in-class pepducin that reversibly inhibits PAR1 (protease-activated receptor 1) on platelets and other vascular cells by targeting intracellular surface receptor. The TRIP-PCI (Thrombin Receptor Inhibitory Pepducin in Percutaneous Coronary Intervention) trial was conducted assess safety efficacy undergoing cardiac catheterization intent perform percutaneous...
12-LOX (12-lipoxygenase) produces a number of bioactive lipids including 12(S)-HETE that are involved in inflammation and platelet reactivity. The GPR31 (G-protein-coupled receptor 31) is the proposed 12(S)-HETE; however, it not known whether 12(S)-HETE-GPR31 signaling axis serves to enhance or inhibit activity. Approach Results: Using pepducin technology biochemical approaches, we provide evidence signals through Gi PAR (protease-activated receptor)-4-mediated activation arterial thrombosis...
Activation of the mineralocorticoid receptor (MR) promotes inflammation, fibrosis, and hypertension. Clinical experimental studies show that MR antagonists have significant therapeutic benefit for all-cause heart failure; however, blockade renal MRs limits their widespread use. Identification key downstream signaling mechanisms in cardiovascular system may enable development targeted with selectivity pathological lower impact on physiological electrolyte handling. One candidate pathway is...
Loss of mineralocorticoid receptor signaling selectively in cardiomyocytes can ameliorate cardiac fibrotic and inflammatory responses caused by excess mineralocorticoids. The aim this study was to characterize the role cardiomyocyte ischemia–reperfusion injury recovery identify a modulation function. Wild-type knockout mice (8 weeks) were uninephrectomized maintained on (1) high salt (0.9% NaCl, 0.4% KCl) or (2) plus deoxycorticosterone pellet (0.3 mg/d, 0.9% KCl). After 8 weeks treatment,...
Objective: Destruction of arterial collagen allows monocyte and macrophage infiltration leading to atherosclerotic plaque formation, but it is not clear what role the MMP1 (matrix metalloprotease 1) collagenase plays in this process vivo. To define specific contribution burden pathogenesis, we generated ApoE −/− mice deficient human ortholog, MMP1a. Approach Results: After 12 16 weeks Western diet, genetic loss MMP1a resulted a significant 50% reduction total aortic compared with control...
We previously identified a critical pathogenic role for MR activation in cardiomyocytes that included potential interaction between the and molecular circadian clock. While glucocorticoid regulation of clock is undisputed, interactions with signalling are limited. hypothesised influences cardiac signalling, vice versa. 10nM aldosterone or corticosterone regulated CRY 1, PER1, PER2 ReverbA (NR1D1) gene expression patterns H9c2 cells over 24hr. MR-dependent promoters containing GREs E-box...
BACKGROUND: PAR1 (protease-activated receptor-1) contributes to acute thrombosis, but it is not clear whether the receptor involved in deleterious inflammatory and profibrotic processes heart failure. Here, we employ pepducin technology determine effects of targeting a mouse failure with reduced ejection fraction model. METHODS: After undergoing transverse aortic constriction pressure overload or sham surgery, C57BL/6J mice were randomized daily sc PZ-128 vehicle, cardiac function,...
Inappropriate mineralocorticoid receptor (MR) activation promotes cardiac tissue inflammation and fibrosis.We identified a critical pathogenic role for MR specifically in cardiomyocytes that revealed potential interaction between the molecular circadian clock. While glucocorticoid regulation of clock is undisputed, interactions with signalling are poorly defined. We hypothesised influences signalling, vice versa. 10nM aldosterone or corticosterone regulated CRY 1, PER1, PER2 andReverbA...