A5053427226- Chronic Obstructive Pulmonary Disease (COPD) Research
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Renin-Angiotensin System Studies
- Protease and Inhibitor Mechanisms
- Cardiovascular Disease and Adiposity
- Cardiac Ischemia and Reperfusion
- Signaling Pathways in Disease
- Neonatal Respiratory Health Research
- Cardiac Fibrosis and Remodeling
- Autophagy in Disease and Therapy
- Pulmonary Hypertension Research and Treatments
- Sirtuins and Resveratrol in Medicine
- Neuroscience of respiration and sleep
- Receptor Mechanisms and Signaling
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Immunotherapy and Immune Responses
- Transplantation: Methods and Outcomes
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Hormonal Regulation and Hypertension
- Computational Drug Discovery Methods
- Nitric Oxide and Endothelin Effects
- Phosphodiesterase function and regulation
Tribhuvan University
2002-2024
Henry Ford Health System
2020-2024
Michigan United
2024
University of South Dakota
2018-2023
University of Alberta
2013-2020
Universities of Giessen and Marburg Lung Center
2008-2020
German Center for Lung Research
2014-2020
Cardio-Pulmonary Institute
2020
Nirma (India)
2011-2019
Alberta Hospital Edmonton
2013-2017
Obesity is increasing in prevalence and strongly associated with metabolic cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into 1-7. We studied the role of ACE2 obesity-mediated cardiac dysfunction. null (ACE2KO) wild-type (WT) mice were fed high-fat diet (HFD) or control at 6 months age. Loss resulted decreased weight gain...
Background: Although empagliflozin was shown to profoundly reduce cardiovascular events in diabetic patients and blunt the decline cardiac function nondiabetic mice with established heart failure (HF), mechanism of action remains unknown. Methods Results: We treated 2 rodent models HF 10 mg/kg per day measured activation NLRP3 (nucleotide-binding domain-like receptor protein 3) inflammasome heart. show for first time that beneficial effects reduced ejection fraction (HF [HFrEF]; n=30–34)...
Iron-overload cardiomyopathy is a prevalent cause of heart failure on world-wide basis and major mortality morbidity in patients with secondary iron-overload genetic hemochromatosis. We investigated the therapeutic effects resveratrol acquired models cardiomyopathy. Murine showed cardiac iron-overload, increased oxidative stress, altered Ca(2+) homeostasis myocardial fibrosis resulting disease. nuclear acetylated levels FOXO1 corresponding inverse changes SIRT1 corrected by therapy....
Rationale: The ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway are pivotal to proteostasis. Targeting these pathways is emerging as an attractive strategy for treating cancer. However, a significant proportion of patients who receive proteasome inhibitor-containing regime show cardiotoxicity. Moreover, UPS defects implicated in cardiac pathogenesis. Hence, better understanding cross-talk between 2 catabolic will help advance pathophysiology medicine. Objective:...
Infarction occurs when myocardial perfusion is interrupted for prolonged periods of time. Short episodes ischemia and reperfusion protect against tissue injury the heart subjected to a subsequent ischemic episode, phenomenon known as preconditioning (IPC). Hypoxia-inducible factor 1 (HIF-1) transcription that mediates adaptive responses hypoxia/ischemia required IPC. In this study, we performed cellular molecular characterization role HIF-1 in We analyzed mice with knockout HIF-1α or HIF-1β...
Angiotensin-converting enzyme (ACE) 2 is a key negative regulator of the renin-angiotensin system and metabolizes angiotensin II (Ang II) into Ang 1 to 7. vasoactive peptide, which plays an important role in vascular disease. The objective present study was define ACE2 pathological remodeling. We found upregulation dilated human aorta with bicuspid aortic valve murine response II. Ex vivo pressure myography showed increased stiffness knockout (KO) mesenteric arteries (1.5 mg/kg per day)...
Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. No therapy stopping progress the available.To investigate role soluble guanylate cyclase (sGC)-cGMP axis in development lung emphysema and hypertension (PH) to test whether sGC-cGMP treatment target for these conditions.Investigations were performed human tissue from patients with COPD, healthy donors, mice, guinea pigs. Mice exposed cigarette smoke (CS) 6 hours per day, 5 days week up months treated BAY...
Oral administration of resveratrol attenuates several symptoms associated with the metabolic syndrome, such as impaired glucose homeostasis and hypertension. Recent work has shown that can improve in obesity via changes gut microbiota. Studies involving fecal microbiome transplants (FMTs) suggest either live microbiota or bacterial-derived metabolites from ingestion are responsible for producing observed benefits recipients. Herein, we show obese mice receiving FMTs healthy resveratrol-fed...
PDE1 inhibition enhances the proteasome and protects against proteinopathy heart failure with preserved ejection fraction.
Myocardial reperfusion after ischemia (I/R), although an effective approach in rescuing the ischemic myocardium, can itself trigger several adverse effects including aberrant remodeling of myocardium and its extracellular matrix. Tissue inhibitor metalloproteinases (TIMPs) protect matrix against excess degradation by (MMPs). TIMP4 levels are reduced myocardial infarction; however, causal role progression post-I/R injury has not been explored.In vivo I/R (20-minute ischemia, 1-week...
Doxorubicin (DOX) is among the most effective chemotherapies used in paediatric cancer patients. However, clinical utility of DOX offset by its well-known cardiotoxicity, which often does not appear until later life. Since hypertension significantly increases risk late-onset heart failure childhood survivors, we investigated whether juvenile exposure impairs ability to adapt angiotensin II (Ang II)-induced life and tested a treatment that could prevent this.Five-week-old male mice were...
Oxidative stress plays a key pathogenic role in experimental and human heart failure. However, the source of ROS (reactive oxygen species) is determinant cardiac adaptation to pathological stressors. In present study, we have shown that dilated cardiomyopathy associated with increased NOX2 (NADPH oxidase 2) levels, oxidative adverse myocardial remodelling activation MAPKs (mitogen-activated protein kinases). Advanced failure mice was also levels. Furthermore, utilized pressure-overload model...
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Cigarette smoking has been identified as one the major risk factors several predisposing genetic have implicated in pathogenesis COPD, including single nucleotide polymorphism (SNP) latent transforming growth factor (TGF)-beta binding protein 4 (Ltbp4)-encoding gene. Consistent with this finding, mice null mutation short splice variant Ltbp4 (Ltbp4S) develop emphysema that reminiscent COPD....
The molecular and cellular determinants of ventricular tachycardia (VT) in patients with nonischaemic dilated cardiomyopathy (NIDCM) remain poorly defined.We examined 20 NIDCM hearts where VT was reported 10 cases absent cases, using a double-blinded case-control study design, assessed the features adverse myocardial remodelling.Explanted from showed greater hypertrophic changes based on cardiomyocyte cross-sectional area expression disease markers, increased fibrosis which extended into...