Vasodilator-stimulated phosphoprotein protects against vascular inflammation and insulin resistance

Autor: Carole L. Wilson, Francis Kim, Michael W. Schwartz, Sanshiro Tateya, Norma Rizzo-DeLeon, Woo Je Lee, Andrew M. Cheng, Alexander W. Clowes
Rok vydání: 2014
Předmět:
Male
Physiology
Endocrinology
Diabetes and Metabolism
Palmitates
Mice
chemistry.chemical_compound
Enos
Phosphorylation
Aorta
Cells
Cultured
Vascular tissue
Bone Marrow Transplantation
Mice
Knockout
Reverse Transcriptase Polymerase Chain Reaction
Microfilament Proteins
Articles
medicine.symptom
Signal Transduction
Vasculitis
medicine.medical_specialty
Nitric Oxide Synthase Type III
Inflammation
macromolecular substances
Biology
Diet
High-Fat
Nitric Oxide
Nitric oxide
Insulin resistance
Physiology (medical)
Internal medicine
medicine
Animals
Humans
Obesity
Protein kinase B
Gene Expression Profiling
Vasodilator-stimulated phosphoprotein
Endothelial Cells
Phosphoproteins
biology.organism_classification
medicine.disease
Mice
Inbred C57BL
Transplantation
Endocrinology
chemistry
Microvessels
Cattle
Insulin Resistance
Cell Adhesion Molecules
Zdroj: American Journal of Physiology-Endocrinology and Metabolism. 307:E571-E579
ISSN: 1522-1555
0193-1849
DOI: 10.1152/ajpendo.00303.2014
Popis: Among the pleotropic effects of endothelial nitric oxide (NO) is protection against vascular inflammation during high-fat diet (HFD) feeding. The current work investigated the role of the enzyme vasodilatory-stimulated phosphoprotein (VASP) as a downstream mediator of the anti-inflammatory effect of NO signaling in vascular tissue. Relative to mice fed a low-fat diet (LFD), levels of VASP Ser239 phosphorylation, a marker of VASP activation, were dramatically reduced in aortic tissue of mice with obesity induced by consuming a HFD. As reported previously, the effect of the HFD was associated with increased aortic inflammation, as measured by increased NF-κB-dependent gene expression, and reduced vascular insulin sensitivity (including insulin-stimulated phosphorylation of eNOS and Akt). These effects of the HFD were recapitulated by VASP knockout, implying a physiological role for VASP to constrain inflammatory signaling and thereby maintain vascular insulin sensitivity. Conversely, overexpression of VASP in endothelial cells blocked inflammation and insulin resistance induced by palmitate. The finding that transplantation of bone marrow from VASP-deficient donors into normal recipients does not recapitulate the vascular effects of whole body VASP deficiency suggests that the protective effects of this enzyme are not mediated in immune or other bone marrow-derived cells. These studies implicate VASP as a downstream mediator of the NO/cGMP pathway that is both necessary and sufficient to protect against vascular inflammation and insulin resistance. As such, this work identifies VASP as a potential therapeutic target in the treatment of obesity-related vascular dysfunction.
Databáze: OpenAIRE
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