A5064521237- Cardiac Valve Diseases and Treatments
- Extracellular vesicles in disease
- Aortic Disease and Treatment Approaches
- Atherosclerosis and Cardiovascular Diseases
- Infective Endocarditis Diagnosis and Management
- Parathyroid Disorders and Treatments
- Cardiac Imaging and Diagnostics
- Lipoproteins and Cardiovascular Health
- Aortic aneurysm repair treatments
- Cell Adhesion Molecules Research
- Cardiovascular Function and Risk Factors
- Cardiovascular Disease and Adiposity
- Protease and Inhibitor Mechanisms
- MicroRNA in disease regulation
- Electrospun Nanofibers in Biomedical Applications
- Coronary Interventions and Diagnostics
- Aortic Thrombus and Embolism
- Congenital heart defects research
- Connective tissue disorders research
- Cerebrovascular and Carotid Artery Diseases
- Tissue Engineering and Regenerative Medicine
- Bone and Dental Protein Studies
- Cardiac Fibrosis and Remodeling
- Cardiomyopathy and Myosin Studies
- Immune cells in cancer
Brigham and Women's Hospital
2016-2025
Harvard University
2016-2025
Woman's Hospital
2011-2024
Center for Excellence in Education
2014-2023
Sechenov University
2019-2022
North American Vascular Biology Organization
2022
Massachusetts General Hospital
2007-2020
National Center for Mathematics and Interdisciplinary Sciences
2016-2018
Center for Vascular Biology Research
2014-2018
Florida International University
2017-2018
ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions extracellular vesicles (EVs), collective term covering various subtypes cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, many other names. However, specific issues arise when working with these entities, whose size amount often make them difficult to obtain as relatively...
Healing of myocardial infarction (MI) requires monocytes/macrophages. These mononuclear phagocytes likely degrade released macromolecules and aid in scavenging dead cardiomyocytes, while mediating aspects granulation tissue formation remodeling. The mechanisms that orchestrate such divergent functions remain unknown. In view the heightened appreciation heterogeneity circulating monocytes, we investigated whether distinct monocyte subsets contribute specific ways to ischemic injury mouse MI....
Monitoring Monocyte Reservoirs Monocytes are cells of the immune system that recruited to sites tissue injury and inflammation where they help resolve infection important for repair. The bone marrow blood believed be primary reservoirs from which monocytes mobilized after injury. Swirski et al. (p. 612 ; see Perspective by Jia Pamer ) now demonstrate spleen also serves as a critical reservoir during ischemic myocardial in very similar phenotype blood-derived injured heart, represent large...
Extracellular vesicles (EVs) are membraneous released by a variety of cells into their microenvironment. Recent studies have elucidated the role EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, as possible reservoirs biomarkers. These findings generated immense interest, along with an exponential increase molecular data pertaining to EVs. Here, we describe Vesiclepedia, manually curated compendium (lipid, RNA, protein) identified different classes...
Macrophage accumulation participates decisively in the development and exacerbation of atherosclerosis. Circulating monocytes, precursors macrophages, display heterogeneity mice humans, but their relative contribution to atherogenesis remains unknown. We report here that Ly-6Chi monocyte subset increased dramatically hypercholesterolemic apoE–deficient consuming a high-fat diet, with number cells doubling blood every month. monocytes adhered activated endothelium, infiltrated lesions, became...
Background— Arterial calcification is associated with cardiovascular events; however, mechanisms of in atherosclerosis remain obscure. Methods and Results— We tested the hypothesis that inflammation promotes osteogenesis atherosclerotic plaques using vivo molecular imaging apolipoprotein E −/− mice (20 to 30 weeks old, n=35). A bisphosphonate-derivatized near-infrared fluorescent agent (excitation 750 nm) visualized osteogenic activity was otherwise undetectable by x-ray computed tomography....
Background— Noninvasive imaging of adhesion molecules such as vascular cell molecule-1 (VCAM-1) may identify early stages inflammation in atherosclerosis. We hypothesized that a novel, second-generation VCAM-1–targeted agent with enhanced affinity had sufficient sensitivity to enable real-time detection VCAM-1 expression experimental atherosclerosis vivo, quantify pharmacotherapy-induced reductions expression, and activated cells human plaques. Methods Results— In vivo phage display...
Background— Macrophages participate centrally in atherosclerosis, and macrophage markers (eg, CD68, MAC-3) correlate well with lesion severity therapeutic modulation. On the basis of avidity lesional macrophages for polysaccharide-containing supramolecular structures such as nanoparticles, we have developed a new positron emission tomography (PET) agent optimized pharmacokinetics to allow vivo imaging at tracer concentrations. Methods Results— A dextranated DTPA-modified magnetofluorescent...
Background— Matrix metalloproteinases (MMPs) in inflamed atherosclerotic plaques may contribute to extracellular matrix remodeling and the onset of acute thrombotic complications. Methods Results— To test hypothesis that optical molecular imaging with use an activatable near-infrared fluorescence (NIRF) probe can detect enzymatic action MMP plaques, we used a NIRF substrate for gelatinases (MMP-2/gelatinase-A MMP-9/gelatinase-B) apolipoprotein E–deficient (apoE −/− ) mice consumed...
Background— Visualizing early changes in valvular cell functions vivo may predict the future risk and identify therapeutic targets for prevention of aortic valve stenosis. Methods Results— To test hypotheses that (1) stenosis shares a similar pathogenesis to atherosclerosis (2) molecular imaging can detect disease, we used panel near-infrared fluorescence agents map endothelial cells, macrophages, proteolysis, osteogenesis valves hypercholesterolemic apolipoprotein E–deficient mice (30 weeks...
We previously showed that early calcification of atherosclerotic plaques associates with macrophage accumulation. Chronic renal disease and mineral imbalance accelerate the subsequent release matrix vesicles (MVs), precursors microcalcification.We tested hypothesis macrophage-derived MVs contribute directly to microcalcification.Macrophages associated regions calcified vesicular structures in human carotid (n=136 patients). In vitro, macrophages released high aggregation potential. expressed...
Background— The evolution of cell phenotypes and matrix architecture in cardiac valves during fetal maturation postnatal adaptation through senescence remains unexplored. Methods Results— We hypothesized that valvular interstitial (VIC) endothelial (VEC) phenotypes, critical for maintaining valve function, change throughout life response to environmental stimuli. performed quantitative histological assessment 91 human semilunar obtained from fetuses at 14 19 20 39 weeks’ gestation; neonates...
Abstract Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of vesicular nomenclatures and components, online searches for EV-related publications components currently challenging. Results: We present an improved version EVpedia, a public database EVs research. This community web portal contains identification orthologous bioinformatic tools personalized function. EVpedia includes 6879 publications, 172...
Monocytes participate importantly in the pathogenesis of atherosclerosis, but their spatial and temporal recruitment from circulation remains uncertain. This study tests hypothesis that monocyte accumulation atheroma correlates with extent disease by using a sensitive simple quantitative assay allows tracking highly enriched populations blood monocytes. A two-step isolation method yielded viable functionally intact peripheral (>90%). Recipient mice received syngeneic monocytes labeled two...
Using 2.1-µm high-resolution microcomputed tomography, we have examined the spatial distribution, clustering, and shape of nearly 35,000 microcalcifications (µCalcs) ≥ 5 µm in fibrous caps 22 nonruptured human atherosclerotic plaques. The vast majority these µCalcs were <15 invisible at previously used 6.7-µm resolution. A greatly simplified 3D finite element analysis has made it possible to quickly analyze which thousands minute inclusions are potentially dangerous. We show that enhancement...
Inflammation can extend ischemic brain injury and adversely affect outcome in experimental animal models. A key difficulty translating studies to humans is the lack of a definitive method confirm track inflammation vivo. Myeloperoxidase (MPO), inflammatory enzyme secreted by activated neutrophils macrophages/microglia, generate highly reactive oxygen species cause additional damage cerebral ischemia. We report here that functional, enzyme-activatable MRI agent accurately oxidative activity...
Background— Clinical studies have demonstrated that 50% of individuals with chronic renal disease (CRD) die cardiovascular causes, including advanced calcific arterial and valvular disease; however, the mechanisms accelerated calcification in CRD remain obscure, no therapies can prevent progression. We recently vivo inflammation triggers calcification. In vitro evidence also indicates elastin degradation products may promote osteogenesis. Here, we used genetically modified mice molecular...