A5075927222- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Telomeres, Telomerase, and Senescence
- Parathyroid Disorders and Treatments
- Signaling Pathways in Disease
- Systemic Lupus Erythematosus Research
- Cardiac Fibrosis and Remodeling
- Genetics, Aging, and Longevity in Model Organisms
- Blood Coagulation and Thrombosis Mechanisms
- Asthma and respiratory diseases
- Cardiovascular Disease and Adiposity
- Cardiomyopathy and Myosin Studies
- Antioxidant Activity and Oxidative Stress
- Nutrition, Genetics, and Disease
- Enzyme Structure and Function
- Microbial metabolism and enzyme function
- Biomarkers in Disease Mechanisms
- Cytokine Signaling Pathways and Interactions
- Biocrusts and Microbial Ecology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ovarian function and disorders
- Spaceflight effects on biology
- Atherosclerosis and Cardiovascular Diseases
- Reproductive System and Pregnancy
- Microbial Metabolic Engineering and Bioproduction
Northwestern University
2013-2023
Renal Research Institute
2019-2022
Marmara University
2018
Indiana Hemophilia and Thrombosis Center
2017
Jesse Brown VA Medical Center
2017
Cardiovascular Institute Hospital
2016
Dr. Siyami Ersek Göğüs Kalp Ve Damar Cerrahisi Eğitim Ve Araştırma Hastanesi
2015
Tohoku University
2013
Sanford Burnham Prebys Medical Discovery Institute
2013
Vanderbilt University
2002-2007
Significance Plasminogen activator inhibitor-1 (PAI-1) is an essential mediator of cellular senescence in vitro and one the biochemical fingerprints vivo. Klotho -deficient ( kl/kl ) mice display a complex phenotype reminiscent human aging exhibit age-dependent increases PAI-1 tissues plasma. Thus, we hypothesized that contributes to aging-like mice. We observed either genetic deficiency or pharmacological inhibition was associated with reduced evidence senescence, preserved organ structure...
Humans with a rare gene mutation in SERPINE1 live longer and show evidence of protection from aging-related morbidity.
Long-term inhibition of nitric oxide synthase by L-arginine analogues such as N(ω)-nitro-l-arginine methyl ester (L-NAME) has been shown to induce senescence in vitro and systemic hypertension arteriosclerosis vivo. We previously reported that plasminogen activator inhibitor-1 (PAI-1)-deficient mice (PAI-1(-/-)) are protected against L-NAME-induced pathologies. In this study, we investigated whether a novel, orally active PAI-1 antagonist (TM5441) similar protective effect L-NAME treatment....
Plasminogen activator inhibitor 1 (PAI-1) is a functional biomarker of the metabolic syndrome. Previous studies have demonstrated that PAI-1 mechanistic contributor to several elements syndrome, including obesity, hypertension and insulin resistance. Here we show also critical regulator hepatic lipid metabolism. RNA sequencing revealed directly regulates transcriptional expression numerous genes involved in mammalian homeostasis, PCSK9 FGF21. Pharmacologic or genetic reductions plasma...
Plasminogen activator inhibitor-1 (PAI-1) regulates fibrinolysis and has been reported to be an independent risk factor for ischemic cardiovascular events. This study describes the age-dependent development of spontaneous coronary arterial thrombi that are associated with evidence subendocardial myocardial infarction in mice transgenic human PAI-1.We generated two founder lines express a stable variant active PAI-1 under control murine preproendothelin-1 (mPPET-1) promoter. Backcrossed...
X-ray analyses of wild-type and mutant flavodoxins from Clostridium beijerinckii show that the conformation peptide Gly57-Asp58, in a bend near isoalloxazine ring FMN, is correlated with oxidation state FMN prosthetic group. The Gly-Asp may adopt any three conformations: trans O-up, which carbonyl oxygen Gly57 (O57) points toward flavin ring; O-down, O57 away flavin; cis O-down. Interconversions among these conformers are linked to oxidation-reduction can modulate redox potentials bound FMN....
Inhibition of the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) or depletion sarcoplasmic reticulum (SR) Ca(2+) stores protects against apoptosis from excessive isoproterenol (Iso) stimulation in cultured ventricular myocytes, suggesting that CaMKII inhibition could be a novel approach to reducing cell death conditions increased adrenergic tone, such as myocardial infarction (MI), vivo. We used mice with genetic due transgenic expression highly specific inhibitory...
// Asish K. Ghosh 1 , Rahul Rai Kitae E. Park Mesut Eren Toshio Miyata 2 Lisa D. Wilsbacher and Douglas Vaughan Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, Illinois, USA United Centers for Advanced Translational Tohoku University, Miyagi, Japan Correspondence to: Vaughan, email: Ghosh, Keywords : cellular senescence, doxorubicin, cardiomyocytes, fibroblasts, endothelial cells, Gerotarget Received June 15, 2016 Accepted September 29,...
Fibrosis is the pathological consequence of stress-induced tissue remodeling and matrix accumulation. Increased levels plasminogen activator inhibitor type I (PAI-1) have been shown to promote fibrosis in multiple organ systems. Paradoxically, homozygous genetic deficiency PAI-1 associated with spontaneous age-dependent, cardiac-selective mice. We identified a novel PAI-1-dependent mechanism that regulates cardiomyocyte-derived fibrogenic signals cardiac transcriptional pathways during...
Aging drives the occurrence of numerous diseases, including cardiovascular disease (CVD). Recent studies indicate that blood from young mice reduces age-associated pathologies. However, "anti-aging" factors in juvenile circulation remain poorly identified. Here, we characterize role apelinergic axis mammalian aging and identify apelin as an anti-aging factor. The expression (apln) its receptor (aplnr) exhibits age-dependent decline multiple organs. Reduced apln signaling perturbs organismal...
Epigenetic dysregulation plays a crucial role in cardiovascular diseases. Previously, we reported that acetyltransferase p300 (ATp300) inhibitor L002 prevents hypertension-induced cardiac hypertrophy and fibrosis murine model. In this short communication, show treatment of hypertensive mice with ATp300-specific small molecule or C646 reverses left ventricular hypertrophy, diastolic dysfunction, without reducing elevated blood pressures. Biochemically, also reverse histone acetylation...
The BMAL2 gene encodes a member of the basic helix-loop-helix PER-ARNT-SIM family transcription factors, which control diverse physiological processes including circadian rhythms. We identified four novel human transcripts that differ by alternative splicing within their NH 2 -terminal regions. Divergent expression these and previously reported was observed among tissues. functional consequences for transcriptional activation CLOCK:BMAL2 heterodimers were assessed using luciferase reporter...
Drug eluting stents (DES) reduce the incidence of restenosis after coronary angioplasty. Enthusiasm has been tempered by a possible increased risk in-stent thrombosis. We examined effects paclitaxel and rapamycin on endothelial transcriptome to identify alterations in gene expression associated with thrombosis.Gene profiling was performed human artery cells treated or paclitaxel. Plasminogen activator inhibitor-1 (PAI-1) most consistently induced transcript rapamycin-treated cells. RT-PCR...
We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored therapeutic utility blocking PAI-1 preventing airway remodeling, using a specific inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections OVA on Days 0, 3, and 6. Starting Day 11, challenged phosphate-buffered saline or by nebulization three times per week for 4 weeks. Tiplaxtinin...
Alveolar epithelial cell (AEC) apoptosis and inadequate repair resulting from “exaggerated” lung aging mitochondrial dysfunction are critical determinants promoting fibrosis. α-Klotho, which is an antiaging molecule that expressed predominantly in the kidney secreted blood, can protect cells against hyperoxia-induced apoptosis. We reasoned Klotho protects AEC exposed to oxidative stress part by maintaining DNA (mtDNA) integrity mitigating find levels decreased both serum alveolar type II...
Pharmacological inhibition of PAI-1 augments proteolytic clearance FGF23.
To investigate the molecular mechanisms involved in estrogen-dependent control of plasminogen activator inhibitor-1 (PAI-1) gene expression vascular cells, we compared transactivation properties estrogen receptors (ERalpha and ERbeta) regulating activity a human PAI-1 promoter reporter construct transfected bovine aortic endothelial cells (BAECs). ERalpha increased BAECs by an mechanism, whereas ERbeta suppressed estrogen-independent mechanism. The suppressive was dominant over inductive...