A5060576956- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Cellular Mechanics and Interactions
- Atherosclerosis and Cardiovascular Diseases
- Antiplatelet Therapy and Cardiovascular Diseases
- Platelet Disorders and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Acute Myocardial Infarction Research
- Nitric Oxide and Endothelin Effects
- Protein Kinase Regulation and GTPase Signaling
- Coronary Interventions and Diagnostics
- Protease and Inhibitor Mechanisms
- Lipoproteins and Cardiovascular Health
- Cardiomyopathy and Myosin Studies
- Bioinformatics and Genomic Networks
- Genetic Associations and Epidemiology
- Blood Coagulation and Thrombosis Mechanisms
- Mesenchymal stem cell research
- Viral-associated cancers and disorders
- Vitamin D Research Studies
- Congenital heart defects research
- MicroRNA in disease regulation
- Redox biology and oxidative stress
- Cardiac Fibrosis and Remodeling
- Blood properties and coagulation
University of Miami
2013-2025
Johns Hopkins University Center for AIDS Research
2019
Epiphany Biosciences (United States)
2019
Sylvester Comprehensive Cancer Center
2014-2019
Université Clermont Auvergne
2012-2014
Dr. John T. Macdonald Foundation
2013
Duke Medical Center
2001-2009
Clinical Research Institute
2002-2009
Center for Vascular Biology Research
2009
Duke University Hospital
2001-2008
NIH 3T3 fibroblasts stably transformed with a constitutively active isoform of p21 Ras , H-Ras V12 (v-H-Ras or EJ-Ras), produced large amounts the reactive oxygen species superoxide (·O 2 − ). ·O production was suppressed by expression dominant negative isoforms Rac1, as well treatment farnesyltransferase inhibitor diphenylene iodonium, flavoprotein inhibitor. The mitogenic activity cells expressing inhibited chemical antioxidant N -acetyl-L-cysteine. Mitogen-activated protein kinase (MAPK)...
Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, it has an important role in platelet aggregation. It known to be involved the pathogenesis of acute coronary syndromes. Previously, we found high frequency particular polymorphism, Pl A2 , gene encoding IIIa kindreds with prevalence premature myocardial infarction.
Atherosclerosis is largely attributed to chronic vascular injury, as occurs with excess cholesterol; however, the effect of concomitant aging remains unexplained. We hypothesize that time in atherosclerosis progression related obsolescence endogenous progenitor cells normally repair and rejuvenate arteries.Here we show treatment bone marrow-derived from young nonatherosclerotic ApoE-/- mice prevents recipients despite persistent hypercholesterolemia. In contrast, marrow older much less...
Epidermal growth factor and platelet-derived can stimulate the production of second messenger inositol trisphosphate in responsive cells, but biochemical pathway for these signaling events has been uncertain because reactions have not reconstituted with purified molecules vitro. A reconstitution is described that requires only factor, its receptor tyrosine kinase activity, soluble phospholipase C-γ1, also small actin-binding protein profilin. Profilin binds to substrate phosphatidylinositol...
In a variety of non-phagocytic cell types, there is marked increase in intracellular levels reactive oxygen species (ROS), including superoxide and H2O2, after ligand stimulation. We demonstrate that NIH 3T3 cells transient expression constitutively activated forms the small GTP-binding proteins Ras or Rac1 leads to significant ROS. An ROS also demonstrated growth factor [platelet-derived (PDGF) epidermal (EGF)] cytokine [tumour necrosis factor-α (TNF-α) interleukin (IL)-1β] stimulation...
Profilin is generally thought to regulate actin polymerization, but the observation that acidic phospholipids dissociate complex of profilin and raised possibility might also lipid metabolism. isolated from platelets binds with high affinity small clusters phosphatidylinositol 4,5-bisphosphate (PIP 2 ) molecules in micelles bilayers other phospholipids. The molar ratio PIP 1:7 pure 1:5 composed largely competes efficiently platelet cytosolic phosphoinositide-specific phospholipase C for...
Homocysteine is a risk factor for the development of atherosclerosis and its thrombotic complications. We have employed an animal model to explore hypothesis that increase in reactive oxygen species subsequent loss nitric oxide bioactivity contribute endothelial dysfunction mild hyperhomocysteinemia. examined function vivo oxidant burden mice heterozygous deletion cystathionine β-synthase (CBS) gene, by studying isolated, precontracted aortic rings mesenteric arterioles situ. CBS–/+...
The signal transduction pathway leading to the activation of transcription factor NF-kappaB remains incompletely characterized. We demonstrate that in HeLa cells, transient expression a constitutively active mutant small GTP-binding protein rac1 (V12rac1) leads significant increase transcriptional activity. In addition, dominant-negative (N17rac1) inhibits basal and interleukin 1beta-stimulated Gel shift analysis using nuclear extract prepared from cells infected with recombinant adenovirus...
Both inherited predisposition and platelet hyperreactivity have been associated with ischemic coronary events, but mechanisms that support genetic differences among platelets from different subjects are generally lacking. Associations between the Pl(A2) polymorphism of GP IIIa syndromes raise question as to whether this variation may contribute hyperreactivity.In study, we characterized functional parameters in healthy donors Pl(A) (HPA-1) polymorphism, a Leu (Pl(A1)) Pro (Pl(A2))...
We present evidence for a new mechanism by which two major actin monomer binding proteins, thymosin beta 4 and profilin, may control the rate extent of polymerization in cells. Both proteins bind monomers transiently with stoichiometry 1:1. When bound to actin, strongly inhibits exchange nucleotide blocking its dissociation, while profilin catalytically promotes exchange. Because both rapidly between molecules, low concentrations can overcome inhibitory effects high on These reactions allow...
Scleroderma is a chronic systemic disease that leads to fibrosis of affected organs. Transforming growth factor (TGF) beta has been implicated in the pathogenesis scleroderma. Smad proteins are signaling transducers downstream from TGF-beta receptors. Three families Smads have identified: (i) receptor-regulated Smad2 and -3 (R-Smads); (ii) common partner Smad4 (Co-Smad); (iii) inhibitory Smad6 -7 (I-Smads, part negative feedback loop). We investigated components for pathway activity...
We have reexamined the interaction of purified platelet profilin with actin and present evidence that simple sequestration monomers in a 1:1 complex cannot explain many effects on assembly. Three different methods to assess binding show has dissociation constant range 1 5 microM. The value for muscle is similar. When bound actin, increases rate ATP from by 1,000-fold also Ca2+ actin. Kinetic simulation showed exchanges between subsecond time scale allows it catalyze nucleotide exchange. On...
Abstract —In a transgenic model of ischemic cardiomyopathy in which monocytes are attracted to the myocardium by targeted overexpression monocyte chemoattractant protein-1 (MCP-1), we have observed presence endothelial NO synthase and platelet cell adhesion molecule-1–negative tunnels, occasionally containing blood-derived cells, that probe cardiac tissue. Immunohistochemical data show monocytes/macrophages (MCs/Mphs) drill tunnels using broad-spectrum mouse macrophage metalloelastase....
Background— Oxidant stress has been implicated in the pathogenesis of atherothrombosis and other vascular disorders accompanied by endothelial dysfunction. Glutathione peroxidases (GPx) play an important role cellular defense against oxidant utilizing glutathione (GSH) to reduce lipid hydroperoxides hydrogen peroxide their corresponding alcohols. Cellular GPx (GPx-1) is principal intracellular isoform GPx. We hypothesized that GPx-1 deficiency per se induces dysfunction structural...
Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but relationship whole blood gene expression changes with disease remains unclear. We have investigated whether patterns peripheral correlate severity these extent atherosclerosis vascular wall. Patients were selected according to their index (CADi), validated angiographical measure that correlates outcome. RNA was extracted from 120 patients at least stenosis greater than...
Rationale: Endothelial progenitor cells (EPCs) contribute to the regeneration of endothelium. Aging-associated senescence results in reduced number and function EPCs, potentially contributing increased cardiac risk, angiogenic capacity, impaired repair effectiveness. The mechanisms underlying EPC are unknown. Increasing evidence supports role microRNAs regulating cellular senescence. Objective: We aimed determine whether regulated and, if so, what are. Methods Results: To map microRNA/gene...
Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal cells (allo-hMSCs) exert immunomodulatory effects promote tissue repair. This a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) frailty. The primary endpoint was incidence treatment-emergent serious adverse events (TE-SAEs) at...