T-cadherin Is Essential for Adiponectin-mediated Revascularization*

Abstract

Background: Adiponectin has vascular protective actions and is bound by T-cadherin. Results: T-cadherin-deficient mice lack skeletal muscle tissue-resident adiponectin and display impaired revascularization that is not improved by treatment with exogenous adiponectin. Conclusion: Expression of T-cadherin is critical for revascularization actions of adiponectin in vitro and in vivo.Significance: The T-cadherin/adiponectin interaction is important for vascular homeostasis.

Divergent Roles for Adiponectin Receptor 1 (AdipoR1) and AdipoR2 in Mediating Revascularization and Metabolic Dysfunction in Vivo

“…In a similar study siRNA knockdown of AdipoR1 but not AdipoR2 was found to attenuate the activating phosphorylation of AMP-activated protein kinase after adiponectin treatment (30). In addition, we and others have found that reduced expression of either AdipoR1 or AdipoR2 inhibits adiponectin-mediated endothelial cell migration and proliferation (17), surrogate measures of angiogenesis. Of course, other cell types participate in limb regenerative response to ischemia.…”

“…AdipoR2 Is Necessary for the Revascularization Actions of Adiponectin-We previously reported that hydrodynamic delivery of adiponectin plasmid rescued the impairment in blood flow recovery observed in adiponectin-deficient mice subjected to hind limb ischemia (17). Thus, to test for a functional ligand-receptor interaction between adiponectin and AdipoR2, we determined if treatment with exogenous adiponectin would rescue the impairment in blood flow recovery in AdipoR2-KO mice.…”

“…AdipoR2 is most abundant in white and brown adipose tissue with relatively low transcript levels in cardiovascular tissues. This analysis was also performed on the adiponectin-binding protein, T-cadherin, that has recently been identified as essential for mediating the cardiac-protective and revascularization actions of adiponectin by localizing adiponectin to cardiovascular tissues (17,42). T-cadherin mRNA is abundant in the heart and aorta and comparatively low in metabolically active skeletal muscle and liver tissues (Fig.…”

“…Although there are many studies on AdipoR1 and AdipoR2 function and regulation in cell culture models (for example, see Refs. [12][13][14][15][16][17], relatively few studies have explored their roles in mouse genetic models. Yamauchi et al (18) reported that deficiency of AdipoR1, AdipoR2, or both adiponectin receptors resulted in glucose intolerance in a mouse model of diet-induced obesity.…”

Adipose Tissue as an Endocrine Organ

“…The protective functions of adiponectin are mainly attributed to its anti-diabetic, anti-inflammation, and vascularprotective functions. It is worthy to note that although adiponectin is exclusively expressed in adipocytes, the receptors for adiponectin [39,40], the adipoR1, adipoR2 and T cadherin, are widely expressed throughout the body and thereby facilitate the pleotrophic action of this favorable adipokine. Mechanistically, it was shown that phosphorylation and activation of the 5′-AMP-activated protein kinase (AMPK) are stimulated by adiponectin in skeletal muscle and in the liver [41].…”