A5103104239- Atherosclerosis and Cardiovascular Diseases
- Kruppel-like factors research
- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- Zebrafish Biomedical Research Applications
- Cellular Mechanics and Interactions
- Ferroptosis and cancer prognosis
- Renal and related cancers
- Biomarkers in Disease Mechanisms
- Protease and Inhibitor Mechanisms
- Cancer-related gene regulation
- Lipid metabolism and disorders
- Collagen: Extraction and Characterization
- Phagocytosis and Immune Regulation
- Blood properties and coagulation
- Chemotherapy-induced cardiotoxicity and mitigation
- RNA Research and Splicing
- Diet, Metabolism, and Disease
- Connective Tissue Growth Factor Research
Cleveland Clinic Lerner College of Medicine
2019-2024
Cleveland Clinic
2023-2024
University of Virginia
2007-2019
Cardiovascular Research Center
2018
Vanderbilt University Medical Center
2009
University of Toronto
2009
University of California, Los Angeles
2009
Russian Foundation for Basic Research
2006
Institute of Cytology
2002-2006
Atherosclerosis is a vascular disease characterized by lipid deposition and inflammation within the arterial wall. Oxidized phospholipids (oxPLs), such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) its constituents 1-palmytoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) are concentrated atherosclerotic lesions known to be potent proinflammatory mediators. Phenotypic switching of smooth muscle cells...
Pyroptosis executor GsdmD (gasdermin D) promotes atherosclerosis in mice and humans. Disulfiram was recently shown to potently inhibit GsdmD, but the vivo efficacy mechanism of disulfiram's antiatherosclerotic activity is yet be explored.
Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a critical role in the development atherosclerosis. However, factors present within lesions that mediate VSMC phenotypic are unclear. Oxidized phospholipids (OxPLs), including 1-palmitoyl-2-(5-oxovaleroyl)- sn -glycero-3-phosphorylcholine (POVPC), active components minimally modified low density lipoprotein and have been previously shown induce multiple proatherogenic events endothelial macrophages, but their...
Abstract Aims Until recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role smooth muscle Here, we asked if might play functional regulating endothelial cell (EC) phenotypic modulations atherosclerosis. Methods and results Specifically, show EC-specific Oct4 knockout resulted increased lipid, LGALS3+...
Biological sex differences play a vital role in cardiovascular diseases, including atherosclerosis. The endothelium is critical contributor to pathologies since endothelial cells (ECs) regulate vascular tone, redox balance, and inflammatory reactions. Although EC activation dysfunction an essential the early late stages of atherosclerosis development, little known about sex-dependent EC.
Objective: Smooth muscle cells and pericytes display remarkable plasticity during injury disease progression. Here, we tested the hypothesis that perivascular give rise to Klf4 -dependent macrophage-like augment adipose tissue (AT) inflammation metabolic dysfunction associated with diet-induced obesity (DIO). Approach Results: Using Myh11-Cre ERT2 eYFP (enhanced yellow fluorescent protein) mice flow cytometry of stromovascular fraction epididymal AT, observed a large smooth lineage traced +...
Major myeloid cell functions from adhesion to migration and phagocytosis are mediated by integrin complexes, also known as adhesome. The presence of a direct binding partner Kindlin-3 is crucial for these functions, its lack causes severe immunodeficiency in humans. However, how incorporated into the adhesome function regulated poorly understood. In this study, using nuclear magnetic resonance spectroscopy, we show that directly interacts with paxillin (PXN) leupaxin (LPXN) via G43/L47...
The long-term adverse effects of radiotherapy on cardiovascular disease are well documented. However, the underlying mechanisms responsible for this increased risk poorly understood. Previous studies using rigorous smooth muscle cell (SMC) lineage tracing have shown abundant SMC investment into atherosclerotic lesions, where SMCs contribute to formation a protective fibrous cap. Studies herein tested whether radiation impairs adaptive responses during vascular disease. To do this, we exposed...
Objective: Oxidized phospholipids (OxPL), such as the oxidized derivatives of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine, and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine, have been shown to be principal biologically active components minimally LDL (low-density lipoprotein). The role OxPL in cardiovascular diseases is well recognized, including activation inflammation within vascular cells. Atherosclerotic...
Introduction There is growing evidence that smooth muscle cell ( SMC ) phenotypic transitions play critical roles during normal developmental and tissue recovery processes in pathological conditions such as atherosclerosis. However, the molecular mechanisms responsible for these are not well understood. Recently, we found embryonic stem cell/induced pluripotent iPSC factor OCT4, which was believed to be silenced somatic cells, plays an atheroprotective role SMC, regulates angiogenesis after...
Laminin-2/4 is the major laminin isoform of normal muscle and nerve tissues plays an important role in tumor invasion metastasis. Despite fact that laminin-2/4 has been found skin basement membrane, insufficient evidence available on effect behavior both transformed cells. A comparison contribution alpha2beta1, alpha3beta1, alpha6beta4 integrins 67 kDa receptor surface human epidermoid carcinoma cell, A-431, to interaction with was carried out. The cell extracellular matrix component a...
Objectives: We previously found that the pluripotency factor OCT4 is reactivated in smooth muscle cells (SMC) human and mouse atherosclerotic plaques plays an atheroprotective role. Loss of SMC vitro was associated with decreases migration. However, molecular mechanisms responsible for SMC-OCT4-dependent effects remain unknown. Methods: Since studies embryonic stem demonstrated regulates long non-coding RNAs (lncRNAs) microRNAs (miRNAs), making them candidates effect mediators, we applied...
In the context of atherosclerosis, macrophages exposed to oxidized low-density lipoprotein (oxLDL) exhibit cellular abnormalities, specifically in adhesome functions, yet mechanisms and implications these adhesive dysfunctions remain largely unexplored.
Objectives: There is growing evidence that smooth muscle cell ( SMC ) phenotypic transitions have a critical role in cardiovascular pathologies, including atherosclerosis. However, molecular mechanisms regulating different aspects of these are still not fully elucidated. We previously found the pluripotency factor OCT4 plays protective atherogenesis and neointioma formation after vascular injury. Using bioinformatics approach, we identified Toll-like receptor 4 TLR4 ), an integral component...
Background: Biological sex differences play a critical role in vascular diseases. Using endothelial ( EC ) lineage tracing atherosclerotic mice and cultured mouse human aortic EC, we recently found that female have lower angiogenic potential, higher expression of pro-inflammatory genes intracellular ROS, worse mitochondria functions than male EC. However, the mechanisms responsible for this sexual dimorphism are still unknown. We previously identified pluripotency factor OCT4 as regulator...
Despite decades of research, little is known about mechanisms and factors driving atherosclerotic progression leading to plaque rupture, thrombosis myocardial infarction or stroke. The widely accepted dogma a thin fibrous cap paucity Acta2+ smooth muscle cells (SMC) relative macrophages increases risk rupture. However, our recent rigorous lineage tracing studies in advanced lesions showed subset that express macrophage markers are SMC-derived SMC specific conditional knockout stem...