T-cadherin Is Essential for Adiponectin-mediated Revascularization*

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. Adipose tissue secretes protein factors that have systemic actions on cardiovascular tissues. Previous studies have shown that ablation of the adipocyte-secreted protein adiponectin leads to endothelial dysfunction, whereas its overexpression promotes wound healing. However, the receptor(s) mediating the protective effects of adiponectin on the vasculature is not known. Here we examined the role of membrane protein T-cadherin, which localizes adiponectin to the vascular endothelium, in the revascularization response to chronic ischemia. T-cadherin-deficient mice were analyzed in a model of hind limb ischemia where blood flow is surgically disrupted in one limb and recovery is monitored over 28 days by laser Doppler perfusion imaging. In this model, T-cadherin-deficient mice phenocopy adiponectin-deficient mice such that both strains display an impaired blood flow recovery compared with wild-type controls. Delivery of exogenous adiponectin rescued the impaired revascularization phenotype in adiponectin-deficient mice but not in T-cadherin-deficient mice. In cultured endothelial cells, T-cadherin deficiency by siRNA knockdown prevented the ability of adiponectin to promote cellular migration and proliferation. These data highlight a previously unrecognized role for T-cadherin in limb revascularization and show that it is essential for mediating the vascular actions of adiponectin.

• Publication year

  2013

• Venue

  Journal of Biological Chemistry

• Publication date

  2013-07-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M113.454835PMID 23824191PMCID PMC3750183
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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