Adiponectin at Physiologically Relevant Concentrations Enhances the Vasorelaxative Effect of Acetylcholine via Cav-1/AdipoR-1 Signaling
نویسندگان
چکیده
Clinical studies have identified hypoadiponectinemia as an independent hypertension risk factor. It is known that adiponectin (APN) can directly cause vasodilation, but the doses required exceed physiologic levels several fold. In the current study, we determine the effect of physiologically relevant APN concentrations upon vascular tone, and investigate the mechanism(s) responsible. Physiologic APN concentrations alone induced no significant vasorelaxation. Interestingly, pretreatment of wild type mouse aortae with physiologic APN levels significantly enhanced acetylcholine (ACh)-induced vasorelaxation (P<0.01), an endothelium-dependent and nitric oxide (NO)-mediated process. Knockout of adiponectin receptor 1 (AdipoR1) or caveolin-1 (Cav-1, a cell signaling facilitating molecule), but not adiponectin receptor 2 (AdipoR2) abolished APN-enhanced ACh-induced vasorelaxation. Immunoblot assay revealed APN promoted the AdipoR1/Cav1 signaling complex in human endothelial cells. Treatment of HUVECs with physiologic APN concentrations caused significant eNOS phosphorylation and nitric oxide (NO) production (P<0.01), an effect abolished in knockdown of either AdipoR1 or Cav-1. Taken together, these data demonstrate for the first time physiologic APN levels enhance the vasorelaxative response to ACh by inducing NO production through AdipoR1/Cav-1 mediated signaling. In physiologic conditions, APN plays an important function of maintaining vascular tone.
منابع مشابه
Inducible overexpression of adiponectin receptors highlight the roles of adiponectin-induced ceramidase signaling in lipid and glucose homeostasis
OBJECTIVE Adiponectin and the signaling induced by its cognate receptors, AdipoR1 and AdipoR2, have garnered attention for their ability to promote insulin sensitivity and oppose steatosis. Activation of these receptors promotes the deacylation of ceramide, a lipid metabolite that appears to play a causal role in impairing insulin signaling. METHODS Here, we have developed transgenic mice tha...
متن کاملExpression of Adiponectin Receptors on Peripheral Blood Leukocytes of Hypertensive Children Is Associated with the Severity of Hypertension
The aim of the study was to find out whether peripheral blood leukocyte adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) protein expression patterns (flow cytometry) differ between the primary hypertension children (n = 57) and healthy controls (n = 19) and if their expression levels are related to selected clinical parameters. The group of 26 patients [AdipoR(-)] showed lower and the group of ...
متن کاملC1q/TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1/AMPK/eNOS/nitric oxide signaling pathway.
OBJECTIVE Reduced plasma adiponectin (APN) in diabetic patients is associated with endothelial dysfunction. However, APN knockout animals manifest modest systemic dysfunction unless metabolically challenged. The protein family CTRPs (C1q/TNF-related proteins) has recently been identified as APN paralogs and some CTRP members share APN's metabolic regulatory function. However, the vasoactive pro...
متن کاملPeroxisome Proliferator–Activated Receptor (PPAR) Activation Increases Adiponectin Receptors and Reduces Obesity-Related Inflammation in Adipose Tissue Comparison of Activation of PPAR , PPAR , and Their Combination
We examined the effects of activation of peroxisome proliferator–activated receptor (PPAR) , PPAR , and both of them in combination in obese diabetic KKAy mice and investigated the mechanisms by which they improve insulin sensitivity. PPAR activation by its agonist, Wy-14,643, as well as PPAR activation by its agonist, rosiglitazone, markedly improved insulin sensitivity. Interestingly, dual ac...
متن کاملGlobular Adiponectin, Acting via AdipoR1/APPL1, Protects H9c2 Cells from Hypoxia/Reoxygenation-Induced Apoptosis
Cardiomyocyte apoptosis is an important remodeling event contributing to heart failure and adiponectin may mediate cardioprotective effects at least in part via attenuating apoptosis. Here we used hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cells to examine the effect of adiponectin and cellular mechanisms of action. We first used TUNEL labeling in combination with laser scanning cyto...
متن کامل