A5021940168- Nitric Oxide and Endothelin Effects
- Metabolism, Diabetes, and Cancer
- Cardiac Ischemia and Reperfusion
- Advanced Glycation End Products research
- Protein Kinase Regulation and GTPase Signaling
- Natural Antidiabetic Agents Studies
- Cardiac electrophysiology and arrhythmias
- Adipose Tissue and Metabolism
- Renin-Angiotensin System Studies
- Kruppel-like factors research
- Essential Oils and Antimicrobial Activity
- Ginger and Zingiberaceae research
- Receptor Mechanisms and Signaling
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Ion channel regulation and function
- Lipid metabolism and disorders
- Lipoproteins and Cardiovascular Health
- Piperaceae Chemical and Biological Studies
- Cancer, Lipids, and Metabolism
- Caveolin-1 and cellular processes
- Antioxidant Activity and Oxidative Stress
- Redox biology and oxidative stress
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Metabolomics and Mass Spectrometry Studies
Brigham and Women's Hospital
2005-2017
Harvard University
2005-2017
Beth Israel Deaconess Medical Center
2015
Cardiovascular Research Center
2014
University of Massachusetts Chan Medical School
2013
Universidade Estadual de Maringá
2009
Universidade de São Paulo
2003-2008
Institute of Biomedical Science
2007
European Union of Medical Specialists
2005
Although endothelial dysfunction, defined as abnormal vasoreactivity, is a common early finding in individuals with type 2 diabetes, the endothelium has not been known to regulate metabolism. As PPARγ, transcriptional regulator of energy balance, expressed cells, we set out investigate role cell PPARγ metabolism using mice that lack and BM (γEC/BM-KO). When γEC/BM-KO were fed high-fat diet, they had decreased adiposity increased insulin sensitivity compared control mice, despite serum FFA...
Caveolin-1 is a scaffolding/regulatory protein that interacts with diverse signaling molecules. Caveolin-1null mice have marked metabolic abnormalities, yet the underlying molecular mechanisms are incompletely understood. We found redox stress plasma biomarker 8-isoprostane was elevated in caveolin-1null mice, and discovered siRNA-mediated caveolin-1 knockdown endothelial cells promoted significant increases intracellular H2O2. Mitochondrial ROS production increased after knockdown;...
Endothelial nitric-oxide synthase (eNOS) undergoes a complex pattern of post-translational modifications that regulate its activity. We have recently reported eNOS is constitutively S-nitrosylated in endothelial cells and agonists promote denitrosylation concomitant with enzyme activation (Erwin, P. A., Lin, A. J., Golan, D. E., Michel, T. (2005), J. Biol. Chem. 280, 19888–19894). In the present studies, we use mass spectrometry to confirm zinc-tetrathiolate cysteines are S-nitrosylated....
The immunomodulatory effect of ginger, Zingiber officinale (Zingiberaceae), sage, Salvia officinalis (Lamiaceae) and clove, Syzygium aromaticum (Myrtaceae), essential oils were evaluated by studying humor- cell-mediated immune responses.
Nitric oxide (NO) and hydrogen peroxide (H 2 O ) are synthesized within cardiac myocytes play key roles in modulating cardiovascular signaling. Cardiac contain both the endothelial (eNOS) neuronal (nNOS) NO synthases, but differential of these NOS isoforms interplay reactive oxygen species nitrogen signaling pathways poorly understood. Using a recently developed chemical sensor [Cu (FL2E)] to study adult from wild-type, eNOS null , nNOS mice, we discovered that physiological concentrations H...
These studies explore the connections between simvastatin, Rac1, and AMP-activated protein kinase (AMPK) pathways in cultured vascular endothelial cells arterial preparations isolated from statin-treated mice. In addition to their prominent effects on lipoprotein metabolism, statins can regulate small GTPase may also affect phosphorylation of ubiquitous AMPK. We explored statin-modulated Rac1 AMPK activation both mice as well cells. treated adult with simvastatin daily for 2 weeks then...
Obesity places major demands on the protein folding capacity of endoplasmic reticulum (ER), resulting in ER stress, a condition that promotes hepatic insulin resistance and steatosis. Here we identify transcription factor, Kruppel-like factor 15 (KLF15), as an essential mediator stress-induced liver. Mice with targeted deletion KLF15 exhibit increased inflammation, JNK activation compared to WT mice; however, KLF15-/- mice are protected against fatty liver under high-fat feeding conditions...
Elevated levels of serum retinol-binding protein 4 (RBP4) contribute to insulin resistance and correlate with increased prevalence hypertension myocardial infarction. We sought determine whether lowering RBP4 would improve blood pressure (BP) protect against obesity- or angiotensin (Ang)-II-induced hypertension. Systolic diastolic BP were lower in the RBP4-knockout (RBP4-KO) mice higher RBP4-overexpressing (RBP4-Tg) compared wild-type (WT) littermates. Carbachol-induced vasodilatation was...
Hydrogen peroxide and other reactive oxygen species are intimately involved in endothelial cell signaling. In many types, the AMP-activated protein kinase (AMPK) has been implicated control of metabolic responses, but role redox signaling modulation AMPK remains to be completely defined. We used RNA interference pharmacological methods establish that H(2)O(2) is a critical activator cultured bovine aortic cells (BAECs). treatment BAECs rapidly significantly increases phosphorylation AMPK....
Vasodilator-stimulated phosphoprotein (VASP) is a major substrate for cyclic nucleotide-dependent kinases that has been implicated in cardiac pathology, yet many aspects of VASP's molecular regulation cardiomyocytes are incompletely understood. In these studies, we explored the role VASP, both signaling pathways isolated murine myocytes, as well model hypertrophy VASP(null) mice. We found beta-adrenergic agonist isoproterenol promotes rapid and reversible phosphorylation VASP at Ser157...
MARCKS is an actin-binding protein that modulates vascular endothelial cell migration and cytoskeleton signaling (Kalwa, H., Michel, T. (2011) J. Biol. Chem. 286, 2320-2330). Angiotensin-II a vasoactive peptide implicated in physiology as well pathophysiology; the pathways connecting angiotensin-II cytoskeletal remodeling are incompletely understood. Here we show expressed intact arterial preparations, with prominent staining of endothelium. In cells, angiotensin-II-promoted phosphorylation...
ADP activates a family of cell surface receptors that modulate signaling pathways in broad range cells. receptor antagonists are widely used to treat cardiovascular disease states. These studies identify critical role for the stable reactive oxygen species hydrogen peroxide (H2O2) mediating cellular responses activated by G protein-coupled P2Y1 ADP. We found ADP-dependent phosphorylation key endothelial proteins--including nitric oxide synthase, AMP-activated protein kinase, and...
Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) play key roles in physiological pathological responses cardiac myocytes. The mechanisms whereby H(2)O(2)-modulated phosphorylation pathways regulate the endothelial isoform of nitric synthase (eNOS) these cells are incompletely understood. We show here that H(2)O(2) treatment adult mouse myocytes leads to increases intracellular Ca(2+) ([Ca(2+)](i)), document activity L-type channel is necessary for H(2)O(2)-promoted increase sarcomere...
The aim of this study was to test the hypothesis that vascular dysfunction in neonatal streptozotocin (n-STZ)-induced diabetic rats could be associated with alterations blood pressure, hemodynamic profile, and levels superoxide anion. Diabetes induced by STZ injection (160 mg/kg, i.p.) neonate (2-d-old) Wistar rats. Using intravital microscopy changes mesenteric arteriolar diameters vasoconstrictor agent noradrenaline (NA) anion, measured hydroethidine microfluorography, were determined...
Abstract Hyperglycaemia is a primary cause of vascular complications in diabetes. A hallmark these endothelial cell dysfunction, which partly due to reduced production nitric oxide. The aim this study was verify the influence improved glycaemic control with chlorpropamide on microvascular reactivity, oxide synthase (e-NOS) expression, and NOS activity neonatal streptozotocin-induced diabetic rats (n-STZ). Diabetes induced by STZ injection into neonates Wistar rats. n-STZ were treated (200 mg...
The aim of this study was to investigate the effects HeNe 632.8nm laser on fibroblast content and its influence wound healing process in rats. After a deliberate incision, animals were subjected irradiation with (4J/cm², once day) for periods 1,2,3,4,5,7,9,11,15,21 29 days. histological analysis fibroblasts count analyzed using Image Pro Plus 5 imaging software. promoted decrease irradiated area, suggesting an increase collagen synthesis differentiation. data indicated that interferes process.
The hypoglycemic and antihyperglycemic activities of a hydroethanolic extract prepared from the leaves Averrhoa carambola L. (Oxalidaceae) was evaluated in rats, through experimental models hyperglycemia: type 1 alloxan-induced diabetes, glucose intolerance insulin resistance induced by dexamethasone chronic obesity model sodium monoglutamate. at dosage 800 mg/Kg body weight did not exhibit hyperglycemic tested