A5047359729- Atherosclerosis and Cardiovascular Diseases
- Aortic Disease and Treatment Approaches
- Cardiac Valve Diseases and Treatments
- Single-cell and spatial transcriptomics
- Kruppel-like factors research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Angiogenesis and VEGF in Cancer
- Biomarkers in Disease Mechanisms
- Phagocytosis and Immune Regulation
- Connective tissue disorders research
- Connective Tissue Growth Factor Research
- Cancer-related molecular mechanisms research
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Caveolin-1 and cellular processes
- Adipose Tissue and Metabolism
- Blood Coagulation and Thrombosis Mechanisms
- RNA Research and Splicing
- Congenital heart defects research
- Platelet Disorders and Treatments
- Circular RNAs in diseases
- Eicosanoids and Hypertension Pharmacology
- Cardiovascular Function and Risk Factors
Georgia Institute of Technology
2019-2025
Emory University
2022-2025
The Wallace H. Coulter Department of Biomedical Engineering
2019-2024
Disturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNA-seq) and scATAC-seq study using endothelial-enriched single from the left- right carotid artery exposed to d-flow (LCA) stable-flow (s-flow RCA) mouse partial ligation (PCL) model. We find eight EC clusters along with immune cells, fibroblasts, smooth muscle cells. Analyses of marker genes,...
Objective— Calcific aortic valve (AV) disease, characterized by AV sclerosis and calcification, is a major cause of death in the aging population; however, there are no effective medical therapies other than replacement. calcification preferentially occurs on fibrosa side, exposed to disturbed flow (d-flow), whereas ventricularis side predominantly stable remains protected unclear mechanisms. Here, we tested role novel flow-sensitive UBE2C (ubiquitin E2 ligase C) microRNA-483-3p (miR-483)...
Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow ( d-flow ), while stable s-flow ) are protected. The proatherogenic and atheroprotective effects of mediated part by the global changes endothelial cell (EC) gene expression, which regulates dysfunction, inflammation, atherosclerosis. Previously, we identified kallikrein-related peptidase 10 Klk10 , a secreted serine protease) as flow-sensitive mouse ECs, but its role biology atherosclerosis was...
Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow, and stable flow (s-flow) protects against atherosclerosis by incompletely understood mechanisms.
Background Atherosclerosis occurs preferentially in the arteries exposed to disturbed flow (d-flow), while stable (s-flow) regions are protected even under hypercholesterolemic conditions. We recently showed that d-flow alone initiates flow-induced reprogramming of endothelial cells (FIRE), including novel concept partial endothelial-to-immune-cell-like transition (partial EndIT), but was not validated using a genetic lineage-tracing model. Here, we tested and two-hit hypothesis is an...
Atherosclerosis occurs preferentially in the arteries exposed to disturbed flow (d-flow), while stable (s-flow) regions are protected even under hypercholesterolemic conditions. We recently showed that d-flow alone initiates flow-induced reprogramming of endothelial cells (FIRE), including novel concept partial endothelial-to-immune-cell-like transition (partial EndIT), but was not validated using a genetic lineage-tracing model. Here, we tested and two-hit hypothesis is an initial...
Atherosclerosis is a chronic inflammatory disease and occurs preferentially in arterial regions exposed to disturbed blood flow (d-flow) while the stable (s-flow) are spared. D-flow induces endothelial inflammation atherosclerosis by regulating gene expression partly through flow-sensitive transcription factors (FSTFs). Most FSTFs, including well-known Kruppel-like KLF2 KLF4, have been identified from vitro studies using cultured cells (ECs). Since many genes pathways lost or dysregulated...
Peripheral arterial disease (PAD) is an age-related medical condition affecting mostly muscular arteries of the limb. It 3rd leading cause atherosclerotic morbidity. The mechanical environment endothelial cells (ECs) in PAD characterized by disturbed blood flow (d-flow) and stiff extracellular matrices. In PAD, stiffness due to decreased elastin function increased collagen content. These parameters are largely missing from current models PAD. has been previously proven that ECs exposed...
Abstract Background Cellular communication network factor 3 (CCN3) has been implicated in the regulation of osteoblast differentiation. However, it is not known if CCN3 can regulate valvular calcification. While macrophages have shown to calcification, molecular and cellular mechanisms this process remain poorly understood. In present study, we investigated role macrophage-derived progression calcific aortic valve disease. Methods Myeloid-specific knockout (Mye-CCN3-KO) control mice were...
Atherosclerosis is an inflammatory disease of the arterial regions exposed to disturbed blood flow (d-flow). D-flow regulates expression genes in endothelium at transcriptomic and epigenomic levels, resulting proatherogenic responses. Recently, single-cell RNA sequencing (scRNAseq) Assay for Transposase Accessible Chromatin (scATACseq) studies were performed determine chromatin accessibility changes a resolution using mouse partial carotid ligation (PCL) model. As endothelial cells (ECs)...
HIF1A is significantly upregulated in calcified human aortic valves (AVs). Furthermore, inhibitor PX-478 was shown to inhibit AV calcification under static and disturbed flow conditions. Since elevated stretch one of the major mechanical stimuli for calcification, we investigated effect on collagen turnover a pathophysiological cyclic (15%) condition. Porcine valve (PAV) leaflets were cyclically (1 Hz) stretched at 15% 24 days osteogenic medium with or without PX-478. In addition, PAV...
Background: Calcific aortic valve disease (CAVD) is a highly prevalent disease, especially in the elderly population, but there are no effective drug therapies other than repair or replacement. CAVD develops preferentially on fibrosa side, while ventricularis side remains relatively spared through unknown mechanisms. We hypothesized that prone to due side-dependent differences transcriptomic patterns and cell phenotypes. Methods: To test this hypothesis, we performed single-cell RNA...
Abstract Introduction Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow ( d-flow ), while stable s-flow ) are protected. The proatherogenic and atheroprotective effects of mediated part by the global changes endothelial cell gene expression, which regulates dysfunction, inflammation, atherosclerosis. Previously, we identified Kallikrein-Related Peptidase 10 (KLK10, a secreted serine protease) as flow-sensitive cells, but its role biology...
Atherosclerosis is an inflammatory disease of the arterial regions exposed to disturbed blood flow (d-flow). D-flow regulates expression genes in endothelium at transcriptomic and epigenomic levels, resulting proatherogenic responses. Recently, single-cell RNA sequencing (scRNAseq) Assay for Transposase Accessible Chromatin (scATACseq) studies were performed determine chromatin accessibility changes a resolution using mouse partial carotid ligation (PCL) model. As endothelial cells (ECs)...
Introduction: Atherosclerosis, a leading cause of death worldwide, is chronic inflammatory disease that occurs preferentially in the arterial regions exposed to disturbed flow (d-flow), while those stable (s-flow) are protected. Recently, we reported d- F low I nduced R eprogramming E ndothelial cells (ECs) ( FIRE ), including endothelial inflammation, endothelial-to-mesenchymal transition (EndMT) and endothelial-to-immune-cell (EndIT). Hypothesis: D-flow plus hypercholesterolemia (HighChol)...
Abstract Background Cellular communication network factor 3 (CCN3) has been implicated in the regulation of osteoblast differentiation. However, it is not known if CCN3 can regulate valvular calcification. While macrophages have shown to calcification, molecular and cellular mechanisms this process remain poorly understood. In present study, we investigated role macrophage-derived progression calcific aortic valve disease. Methods Myeloid-specific knockout (Mye-CCN3-KO) control mice were...