A5076897207- Aortic aneurysm repair treatments
- Aortic Disease and Treatment Approaches
- Axon Guidance and Neuronal Signaling
- Atherosclerosis and Cardiovascular Diseases
- Immune cells in cancer
- Apelin-related biomedical research
- Cardiac, Anesthesia and Surgical Outcomes
- Angiogenesis and VEGF in Cancer
- Extracellular vesicles in disease
- MicroRNA in disease regulation
- Adipokines, Inflammation, and Metabolic Diseases
- Protease and Inhibitor Mechanisms
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Peripheral Artery Disease Management
- Phagocytosis and Immune Regulation
- Cholesterol and Lipid Metabolism
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- Cardiovascular Disease and Adiposity
- Connective tissue disorders research
- Lipid metabolism and disorders
- Vascular Procedures and Complications
- Erythrocyte Function and Pathophysiology
- Inflammatory Biomarkers in Disease Prognosis
NYU Langone Health
2013-2025
New York University
2016-2025
Cleveland Clinic Lerner College of Medicine
2014-2024
Brunswick (United States)
2022
Albany Research Institute
2022
Providence College
2022
Ann Arbor Center for Independent Living
2020
Columbia University Irving Medical Center
2018-2019
University of Ottawa
2013-2017
National Research Council Canada
2017
Complicated abdominal aortic aneurysm (AAA) is a major cause of mortality in elderly men. Ang II–dependent TGF-β activity promotes progression experimental Marfan syndrome. However, the role models AAA has not been comprehensively assessed. Here, we show that systemic neutralization breaks resistance normocholesterolemic C57BL/6 mice to II–induced formation and markedly increases their susceptibility disease. These aneurysms displayed large spectrum complications on echography, including...
Atherosclerosis is an inflammatory vascular disease responsible for the first cause of mortality worldwide. Recent studies have clearly highlighted critical role immunoinflammatory balance in modulation development and progression. However, immunoregulatory pathways that control atherosclerosis remain largely unknown. We show loss suppressor cytokine signaling (SOCS) 3 T cells increases both interleukin (IL)-17 IL-10 production, induces antiinflammatory macrophage phenotype, leads to...
Rationale for Study: MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein expression at post-transcriptional level. We hypothesized a specific pool of endothelial miRNAs could be selectively regulated by flow conditions and inflammatory signals, as such involved in the development atherosclerosis. Objective: To identify miRNAs, called atheromiRs, which shear stress oxidized low-density lipoproteins (oxLDL), to determine their role atherogenesis. Methods Results: Large-scale...
Cellular metabolism is increasingly recognized as a controller of immune cell fate and function. MicroRNA-33 (miR-33) regulates cellular lipid represses genes involved in cholesterol efflux, HDL biogenesis, fatty acid oxidation. Here, we determined that miR-33–mediated disruption the balance aerobic glycolysis mitochondrial oxidative phosphorylation instructs macrophage inflammatory polarization shapes innate adaptive responses. Macrophage-specific Mir33 deletion increased respiration,...
Defective autophagy in macrophages leads to pathological processes that contribute atherosclerosis, including impaired cholesterol metabolism and defective efferocytosis. Autophagy promotes the degradation of cytoplasmic components lysosomes plays a key role catabolism stored lipids maintain cellular homeostasis. microRNA-33 (miR-33) is post-transcriptional regulator genes involved homeostasis, yet complete mechanisms by which miR-33 controls lipid are unknown. We investigated whether...
Membrane-shed submicron microparticles (MPs) released following cell activation or apoptosis accumulate in atherosclerotic plaques, where they stimulate endothelial proliferation and neovessel formation. The aim of the study was to assess whether not MPs isolated from human plaques contribute increased adhesion molecules expression monocyte recruitment.Human umbilical vein coronary artery cells were exposed endarterectomy specimens (n=62) characterized by externalized phosphatidylserine....
Endothelial activation and apoptosis release membrane-shed microparticles (EMP) that emerge as important biological effectors.Because laminar shear stress (SS) is a major physiological regulator of endothelial survival, we tested the hypothesis SS regulates EMP release.EMP levels were quantified by flow cytometry in medium cells subjected to low or high (2 20 dyne/cm(2)). augmented with time conditions compared conditions. This effect was sensitive extracellular signal-regulated protein...
Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix (ECM) fragmentation and inflammation. However, the mechanisms which these events coupled thereby fueling focal vascular damage undefined. Here we report through single-cell RNA-sequencing of diseased aorta that neuronal guidance cue netrin-1 can act at interface macrophage-driven injury ECM degradation. Netrin-1 expression peaks in human murine aneurysmal macrophages. Targeted deletion macrophages protects...
Preclinical and clinical studies have shown beneficial effects of infusions apolipoprotein A-I (ApoA-I) on atherosclerosis. ApoA-I is also a target for myeloperoxidase-mediated oxidation, leading in vitro to loss its ability promote ATP-binding cassette transporter A1-dependent macrophage cholesterol efflux. Therefore, we hypothesized that oxidation would impair promotion reverse transport vivo the atherosclerotic plaques.ApoA-I(-/-) or E-deficient mice were subcutaneously injected with...
Objective— The persistence of myeloid-derived cells in the artery wall is a characteristic advanced atherosclerotic plaques. However, mechanisms by which these are retained poorly understood. Semaphorins, class neuronal guidance molecules, play critical role vascular patterning and development, recent studies suggest that they may also have immunomodulatory functions. present study evaluates expression Semaphorin 3E ( Sema3E ) settings relevant to atherosclerosis its contribution macrophage...
Psychological stress (PS) is associated with systemic inflammation and accelerates inflammatory disease progression (e.g., atherosclerosis). The mechanisms underlying stress-mediated future health risk are poorly understood. Monocytes key in sustaining inflammation, recent studies demonstrate that they maintain the memory of insults, leading to a heightened response upon rechallenge. We show PS induces remodeling chromatin landscape transcriptomic reprogramming monocytes, skewing them primed...
During obesity, macrophages infiltrate the visceral adipose tissue and promote inflammation that contributes to type II diabetes. Evidence suggests rewiring of cellular metabolism can regulate macrophage function. However, metabolic programs characterize (ATM) in obesity are poorly defined. Here, we demonstrate ATM from obese mice exhibit profiles characterized by elevated glycolysis oxidative phosphorylation, distinct lean mice. Increased activation HIF-1α resulted induction IL-1β genes...
Abstract Mechanical overload of the vascular wall is a pathological hallmark life-threatening abdominal aortic aneurysms (AAA). However, how this mechanical stress resonates at unicellular level smooth muscle cells (VSMC) undefined. Here we show defective mechano-phenotype signatures VSMC in AAA measured with ultrasound tweezers-based micromechanical system and single-cell RNA sequencing technique. Theoretical modelling predicts that cytoskeleton alterations fuel cell membrane tension VSMC,...
Emerging evidence suggests that neuronal guidance cues, typically expressed during development, are involved in both physiological and pathological immune responses. We hypothesized endothelial expression of such cues may regulate leukocyte trafficking into the vascular wall atherogenesis.We demonstrate members netrin, semaphorin, ephrin family molecules differentially regulated under conditions promote or protect from atherosclerosis. Netrin-1 semaphorin3A by coronary artery cells potently...
Hypoxia is intimately linked to atherosclerosis and has become recognized as a primary impetus of inflammation. We recently demonstrated that the neuroimmune guidance cue netrin-1 (Ntn1) inhibits macrophage emigration from atherosclerotic plaques, thereby fostering chronic However, mechanisms governing expression in are not well understood. In this study, we investigate role hypoxia regulating its receptor uncoordinated-5-B (Unc5b) plaque macrophages functional consequences on these immune...
Obesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, leading cause death worldwide. Although mouse models have provided important insights into the immunopathogenesis various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT) are resistant developing while commonly used genetically modified poor mimics human disease. The lack physiologically relevant experimental model hindered...
Cholesterol homeostasis is fundamental to human health and is, thus, tightly regulated. MicroRNAs exert potent effects on biological pathways, including cholesterol metabolism, by repressing genes with related functions. We reasoned that this mode of pathway regulation could be exploited identify novel involved in homeostasis.Here, we oxysterol-binding protein-like 6 (OSBPL6) as a target 2 miRNA hubs regulating homeostasis: miR-33 miR-27b. Characterization OSBPL6 revealed it...