A5056627231- Extracellular vesicles in disease
- Cardiac Valve Diseases and Treatments
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Aortic Disease and Treatment Approaches
- MicroRNA in disease regulation
- Atherosclerosis and Cardiovascular Diseases
- Lipoproteins and Cardiovascular Health
- Infective Endocarditis Diagnosis and Management
- Parathyroid Disorders and Treatments
- Aortic aneurysm repair treatments
- Dermatological and Skeletal Disorders
- Adipose Tissue and Metabolism
- Vitamin D Research Studies
- Retinoids in leukemia and cellular processes
- Alkaline Phosphatase Research Studies
- Antioxidant Activity and Oxidative Stress
- Cholesterol and Lipid Metabolism
- Bioinformatics and Genomic Networks
- Electrospun Nanofibers in Biomedical Applications
- Single-cell and spatial transcriptomics
- Medical Imaging and Pathology Studies
- Vasculitis and related conditions
- Cardiomyopathy and Myosin Studies
- Acne and Rosacea Treatments and Effects
Brigham and Women's Hospital
2014-2024
Harvard University
2014-2024
Tân Tạo University
2016
National Center for Mathematics and Interdisciplinary Sciences
2016
University of Oklahoma Health Sciences Center
2006-2007
Oklahoma Medical Research Foundation
2007
OU Health
2006
Vascular calcification is a common feature of major cardiovascular diseases. Extracellular vesicles participate in the formation microcalcifications that are implicated atherosclerotic plaque rupture; however, mechanisms regulate calcifying extracellular remain obscure. Here, we have demonstrated sortilin key regulator smooth muscle cell (SMC) via its recruitment to vesicles. Sortilin localized vessels human and mouse atheromata participated SMC culture. regulated loading protein tissue...
Background: No pharmacological therapy exists for calcific aortic valve disease (CAVD), which confers a dismal prognosis without invasive replacement. The search therapeutics and early diagnostics is challenging because CAVD presents in multiple pathological stages. Moreover, it occurs the context of complex, multi-layered tissue architecture; rich abundant extracellular matrix phenotype; unique, highly plastic, multipotent resident cell population. Methods: A total 25 human stenotic valves...
BACKGROUND: Fewer than 50% of patients who develop aortic valve calcification have concomitant atherosclerosis, implying differential pathogenesis. Although circulating extracellular vesicles (EVs) act as biomarkers cardiovascular diseases, tissue-entrapped EVs are associated with early mineralization, but their cargoes, functions, and contributions to disease remain unknown. METHODS: Disease stage–specific proteomics was performed on human carotid endarterectomy specimens (n=16) stenotic...
Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial (ECs) form the innermost lining of all blood vessels, interfacing with in circulation vascular wall. It is unknown whether ECs release EVs capable governing recipient within these 2 separate compartments. Given their boundary location, we propose use bidirectional distinct EV quiescent (healthy) activated (atheroprone) states to communicate vessel
Calcific aortic valve disease (CAVD) occurs when subpopulations of cells undergo specific differentiation pathways, promoting tissue fibrosis and calcification. Lipoprotein particles carry oxidized lipids that promote valvular disease, but low-density lipoprotein–lowering therapies have failed in clinical trials, there are currently no pharmacological interventions available for this disease. Apolipoproteins known promoters atherosclerosis, whether they possess pathogenic properties CAVD is...
Background Peripheral arterial disease (PAD) is estimated to affect 7% of the adult population in United States; however, there currently little understanding key cellular and molecular pathways at play. With PAD characterized by vascular inflammation associated calcification, current study set out elucidate role NLRP3 (nucleotide oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome activation cohort. Methods Results Global proteomics human vessels with...
In calcific aortic valve disease (CAVD), mechanosensitive valvular cells respond to fibrosis- and calcification-induced tissue stiffening, further driving pathophysiology. No pharmacotherapeutics are available treat CAVD because of the paucity (i) appropriate experimental models that recapitulate this complex environment (ii) benchmarking novel engineered (AV)–model performance. We established a biomaterial-based model mimicking biomechanics human AV disease-prone fibrosa layer,...
Calcifying extracellular vesicles (EVs) released from cells within atherosclerotic plaques have received increased attention for their role in mediating vascular calcification, a major predictor of cardiovascular morbidity and mortality. However, little is known about the difference between this pathologic vesicle population other EVs that contribute to physiological cellular processes. One challenge hinders research into these differences inability selectively isolate calcifying...
Lipoprotein(a) (Lp[a]) blood levels >50 mg/dL is a major cardiovascular disease risk factor in humans. Lp(a) associates with increased calcification, critical pathology no clinically available drug therapies. The mechanisms through which increases calcification remain undefined. We hypothesized that promotes the release of calcifying extracellular vesicles (EVs) contribute to formation microcalcification tissues. Here, we show both primary human smooth muscle cells (SMCs) and valvular...
Retinoic acid (RA) is a ligand for nuclear receptors that modulate gene transcription and cell differentiation. Whether RA controls ectopic calcification in humans unknown. We tested the hypothesis regulates osteogenic differentiation of human arterial smooth muscle cells aortic valvular interstitial participate atherosclerosis heart valve disease, respectively. Approach Results: Human cardiovascular tissue contains immunoreactive RAR (RA receptor)-a retinoid-activated receptor directing...
Abstract The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional uptake, storage, metabolism contribute to several major human diseases including atherosclerosis obesity. associates with cardiovascular disease; however, role adipose tissue remains unclear. Here we show that low-density lipoprotein receptor-deficient (Ldlr −/− ) model, deficiency (Sort1 female mice suppresses Niemann-Pick type C1-Like 1 (Npc1l1) mRNA levels, reduces body white...
Significance The most common cause of heart attacks or strokes is the rupture thin fibrous caps that cover vulnerable plaques within blood vessels. Small mineral deposits, called microcalcifications, increase local tissue stress and thereby risk cap rupture. We report here use a three-dimensional collagen hydrogel model calcification complementary mouse plaque formation to determine whether bisphosphonate (BiP) therapy, commonly used treat bone loss, alters microcalcification formation....
Abstract Rationale: Extracellular vesicles (EVs) contain bioactive cargo including microRNAs (miRNAs) and proteins that are released by cells as a form of cell-cell communication. Endothelial (ECs) the innermost lining all blood vessels thereby interface with in circulation well residing vascular wall. It is unknown whether ECs have capacity to release EVs capable governing recipient within two separate compartments, how this affected endothelial activation commonly seen atheroprone regions....
Abstract Calcific aortic valve disease (CAVD) is a complex cardiovascular pathology, culminating in stenosis, heart failure and premature mortality, with no comprehensive treatment strategy, except replacement. While T cells have been identified within the valve, their contribution to pathogenesis remains unclear. To elucidate heterogenous phenotype of immune populations present patients CAVD, deep phenotypic screens paired peripheral blood were conducted via flow cytometry (n=20)...
Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. presence of pigment produced melanocytic population VICs in mice with dark coats has been generally regarded as nuisance, it interferes histological analysis AV However, our previous studies have shown that correlates increased mechanical...
Abstract Background Fewer than 50% of patients develop calcification both atherosclerotic plaques and aortic valves, implying differential pathogenesis. While circulating extracellular vesicles (EVs) act as biomarkers cardiovascular diseases, tissue-entrapped EVs associate with early mineralization, but their contents, function, contributions to disease remain unknown. Results Global proteomics human carotid artery endarterectomies calcified valves from a total 27 donors/patients revealed...
Elevated circulating lipoprotein (a) [Lp(a)] is associated with an increased risk of first and recurrent cardiovascular events; however, the effect baseline Lp(a) levels on long-term outcomes in elderly population not well understood. The current single-center prospective study evaluated association incident acute coronary syndrome to identify populations at future events. concentration was assessed 755 individuals (mean age 71.9 years) within community followed for up 8 years (median time...
Abstract BACKGROUND Calcific aortic valve stenosis (CAVS) is a global clinical burden, impacting around 2% of the population over 65 years age. No pharmacotherapeutics exist, with surgical repair and transcatheter replacement being only intervention. Females are underrepresented in studies CAVS, leading to delay timely intervention increased mortality. Histopathology demonstrates female CAVS presents decreased valvular calcification but fibrosis severity symptoms. We hypothesize that...
Background: No pharmacological therapy exists for calcific aortic valve disease (CAVD), which confers a dismal prognosis without replacement. The search therapeutics and early diagnostics is challenging since CAVD presents in multiple pathological stages. Methods: A total of 25 human stenotic valves obtained from replacement surgery were analyzed by modalities, including transcriptomics global unlabeled tandem-mass-tagged proteomics liquid chromatography-mass spectrometry. Results: Global...
Objective: The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional uptake, storage, metabolism contribute to several major human diseases including atherosclerosis obesity. associates with cardiovascular disease; however, role adipose tissue remains unclear. Approach Results: Here we show that low-density lipoprotein receptor-deficient (Ldlr -/- ) model, deficiency ( Sort1 female mice inhibits intestinal Niemann-Pick type C1-Like 1 (Npc1l1)...
Background: Studying atherosclerotic calcification in vivo requires mouse models with genetic deletion of low-density lipoprotein receptor (Ldlr) or apolipoprotein E. A previous study showed a rapid induction atherosclerosis by proprotein convertase subtilisin/kexin type 9 (PCSK9) mice. Here, we hypothesize that this method is useful tool to cardiovascular non-genetically modified C57BL/6 Results: 10 week old mice received single tail vein injection recombinant adeno-associated viral vector...