Adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice

Abstract

; db/db) mice and studied vascular function of the aorta ex vivo. Ad-APN improved endothelial-dependent vasodilation in db/db mice compared with Ad␤gal, whereas Ad-APN had no further improvement on endothelial function in control mice. This improvement was completely inhibited by a nitric oxide synthase inhibitor (N G -nitro-L-arginine methyl ester). Serum triglyceride and total cholesterol levels were increased in db/db mice, and Ad-APN significantly reduced triglyceride levels but not total cholesterol levels. Immunoblot results showed that interferon-␥, gp91 phox , and nitrotyrosine were markedly increased in the aorta of db/db mice. Ad-APN treatment decreased the expression of these proteins. In addition, mRNA expression of TNF-␣, IL-6, and ICAM-1 was elevated in db/db mice, and Ad-APN treatment decreased these expressions in the aorta. Our findings suggest that APN may contribute to an increase in nitric oxide bioavailability by decreasing superoxide production as well as by inhibiting inflammation and adhesion molecules in the aorta in type 2 diabetic mice. cardiovascular disease; adipokine; superoxide; vascular biology; adenovirus

Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin

“…AdipoQ is a protective adipokine secreted from adipose tissue. Deletion of AdipoQ causes impaired endothelium-dependent relaxation by enhancing oxidative stress and reducing NO bioavailability (32,50), whereas AdipoQ supplementation improved endothelial dysfunction in diabetic mice by suppressing oxidative stress (51). AdipoQ has also been reported to be expressed in kidney (52) and endothelium (33).…”

Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function

“…6) suggests that the CSA end point may allow intervention trials with smaller sample sizes or detection of smaller group differences than the CBF end point. Furthermore, this MRI-IHE approach may facilitate the translation from the bench to the bedside of novel agents (6,14) that may be safely and noninvasively tested in humans.…”

Lipotoxicity contributes to endothelial dysfunction: A focus on the contribution from ceramide

“…[69] Thus it is possible that the balance of SIP and ceramide may influence endothelial function. While adiponectin delivery to mice with T2DM can improve arterial vasorelaxation by increasing NO bioavailability[70], it remains to be determined whether the mechanism is dependent upon generation of SIP from ceramide in the vasculature. Studies investigating this pathway in physiologically relevant scenarios wherein adiponectin is increased (exercise training) or decreased (T2DM) would also be of great interest.…”