A5100327829- Signaling Pathways in Disease
- Cardiac Fibrosis and Remodeling
- Melanoma and MAPK Pathways
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Protein Kinase Regulation and GTPase Signaling
- Autophagy in Disease and Therapy
- Nuclear Receptors and Signaling
- Peptidase Inhibition and Analysis
- Cardiovascular Function and Risk Factors
- Cardiac electrophysiology and arrhythmias
- ATP Synthase and ATPases Research
- Viral Infectious Diseases and Gene Expression in Insects
- Electrophoretic Deposition in Materials Science
- Advanced Glycation End Products research
- Cardiomyopathy and Myosin Studies
- Atherosclerosis and Cardiovascular Diseases
- Cardiovascular Disease and Adiposity
- Protein Tyrosine Phosphatases
- Pharmacological Receptor Mechanisms and Effects
- Heat shock proteins research
- TiO2 Photocatalysis and Solar Cells
- Pancreatic function and diabetes
- Ion channel regulation and function
- RNA regulation and disease
University of Manchester
2016-2025
Jinzhou Medical University
2024
Brigham and Women's Hospital
2019
Harvard University
2019
Manchester Academic Health Science Centre
2019
Harbin Medical University
2017
University of Oxford
2015
New York Institute of Technology
2015
University of Hong Kong
2015
University of Illinois Chicago
2011-2013
Hydrogen sulfide (H2S) has been shown to have powerful antioxidative and anti-inflammatory properties that can regulate multiple cardiovascular functions. However, its precise role in diabetes-accelerated atherosclerosis remains unclear. We report here H2S reduced aortic atherosclerotic plaque formation with reduction superoxide (O2 (-)) generation the adhesion molecules streptozotocin (STZ)-induced LDLr(-/-) mice but not LDLr(-/-)Nrf2(-/-) mice. In vitro, inhibited foam cell formation,...
S-nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in the pathogenesis of cardiovascular disease. The aim this study was to determine role SNO MLP (muscle LIM protein) myocardial hypertrophy, as well mechanism by which SNO-MLP modulates hypertrophic growth response pressure overload.Myocardial samples from patients and animal models exhibiting hypertrophy were examined for level using biotin-switch methods. sites further identified through liquid...
Background Heart failure with preserved ejection fraction (HFpEF) is linked to prolonged endoplasmic reticulum (ER) stress. P21‐activated kinase 2 (Pak2) facilitates a protective ER stress response. This study explores the mechanism and role of Pak2 in HFpEF pathology. Methods Results The mouse model was established using high‐fat diet combined nitric oxide synthase inhibitor Nω‐Nitro‐ l ‐arginine methyl ester (high‐fat diet+Nω‐Nitro‐ ester). exhibited typical characteristics (cardiac...
Background— Stress-induced hypertrophic remodeling is a critical pathogenetic process leading to heart failure. Although many signal transduction cascades are demonstrated as important regulators facilitate the induction of cardiac hypertrophy, signaling pathways for suppressing remain largely unexplored. In this study, we identified p21-activated kinase 1 (Pak1) novel regulator that antagonizes hypertrophy. Methods and Results— Hypertrophic stress applied primary neonatal rat cardiomyocytes...
We investigated whether plasma long-chain sphingoid base (LCSB) concentrations are altered by transient cardiac ischemia during percutaneous coronary intervention (PCI) in humans and examined the signaling through sphingosine-1-phosphate (S1P) cascade as a mechanism underlying S1P cardioprotective effect myocytes. Venous samples were collected from either sinus (n = 7) or femoral vein 24) of 31 patients at 1 5 min 12 h, following induction myocardial elective PCI. Coronary levels LCSB...
Abstract The prevalence of cardiomyopathy from metabolic stress has increased dramatically; however, its molecular mechanisms remain elusive. Here, we show that extracellular signal-regulated protein kinase 5 (Erk5) is lost in the hearts obese/diabetic animal models and cardiac-specific deletion Erk5 mice (Erk5-CKO) leads to dampened cardiac contractility mitochondrial abnormalities with repressed fuel oxidation oxidative damage upon high fat diet (HFD). regulation peroxisome...
Secreted and membrane-bound proteins, which account for 1/3 of all play critical roles in heart health disease. The endoplasmic reticulum (ER) is the site synthesis, folding, quality control these proteins. Loss ER homeostasis function underlies pathogenesis many forms disease.To investigate mechanisms responsible regulating cardiac function, to explore therapeutic potentials strengthening treat disease.Screening a range signaling molecules led discovery that Pak (p21-activated kinase)2...
Abstract The heart responds to pathological overload through myocyte hypertrophy. Here we show that this response is regulated by cardiac fibroblasts via a paracrine mechanism involving plasma membrane calcium ATPase 4 (PMCA4). Pmca4 deletion in mice, both systemically and specifically fibroblasts, reduces the hypertrophic pressure overload; however, knocking out cardiomyocytes does not produce effect. Mechanistically, lacking PMCA4 higher levels of secreted frizzled related protein 2...
Endoplasmic reticulum (ER) stress is increasingly recognized as an important causal factor of many diseases. Targeting ER has now emerged a new therapeutic strategy for treating cardiovascular Here, we investigated the effects and underlying mechanism ginkgolide K (1,10-dihydroxy-3,14-didehydroginkgolide, GK) on cardiac stress.
The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine role immunosenescence diabetic and investigate underlying mechanisms.
The signaling mechanism by which JNK affects mitochondria is critical to initiate apoptosis. Here we show that the absence of provides a partial resistance toxic effect heavy metal cadmium. Both wild type and jnk −/− fibroblasts undergoing death exhibit cytosolic cytochrome c but, unlike cells, JNK‐deficient do not display increased caspase activity DNA fragmentation. apoptotic correlates with specific defect in activation Bax. We conclude JNK‐dependent regulation Bax essential mediate...
Mitogen-activated protein kinase (MAPK) pathways provide a critical connection between extrinsic and intrinsic signals to cardiac hypertrophy. Extracellular signal-regulated (ERK)5, an atypical MAPK is activated in the heart by pressure overload. However, role of ERK5 plays regulating hypertrophic growth hypertrophy-induced apoptosis not completely understood.Herein, we investigate vivo signaling mechanism whereby regulates hypertrophy apoptosis.We generated examined phenotypes mice with...
Background— Hypertension or aortic stenosis causes pressure overload, which evokes hypertrophic myocardial growth. Sustained cardiac hypertrophy eventually progresses to heart failure. Growing evidence indicates that restraining could be beneficial; here, we discovered FTY-720, an immunomodulator for treating multiple sclerosis, can reverse existing hypertrophy/fibrosis. Methods and Results— Male C57/Bl6 mice underwent transverse constriction (TAC) 1 week followed by FTY-720 treatment 2...
Mitogen-activated protein kinase (MKK)4 is a critical member of the mitogen-activated family. It able to activate c-Jun NH(2)-terminal (JNK) and p38 in response environmental stresses. JNK are strongly implicated pathological cardiac hypertrophy heart failure; however, regulatory mechanism whereby upstream MKK4 activates these signaling cascades unknown. To elucidate biological function MKK4, we generated mice with myocyte-specific deletion mkk4 (MKK4(cko) mice). In pressure overload or...
The c-Jun NH2-terminal protein kinase (JNK) is a mitogen-activated (MAPK) involved in the regulation of various physiological processes. Its activity increased upon phosphorylation by MAPK kinases MKK4 and MKK7. early embryonic death mice lacking an mkk4 or mkk7 gene has provided genetic evidence that MKK7 have nonredundant functions vivo. To elucidate role MKK4, we generated novel mouse model which could be specifically deleted brain. At birth, mutant were indistinguishable from their...
Cardiomyocyte apoptosis is one of the key events in development and progression heart failure, a crucial role for ICER (inducible cAMP early repressor) this process has been previously reported. ERK5 known to inhibit cardiac after myocardial infarction (MI), especially hyperglycemic states, via association with CHIP ubiquitin (Ub) ligase subsequent upregulation activity, which induces ubiquitination protein degradation. The regulatory mechanism governing ERK5/CHIP interaction unknown.
In this article the results of an experimental study comparing gas generation in natural ester transformer liquid FR3 and mineral oil Gemini X, under PD sparking faults, are presented. The total amounts fault gases were reported microliters rather than parts per million. show that key generated faults hydrogen acetylene, both X FR3. This finding suggests conventional methods for diagnosing also applicable to Although volume was more 50 times higher unit energy is similar two liquids. Thus it...