非表示:
キーワード:
Adiponectin/genetics/*metabolism
Animals
Cadherins/genetics/*metabolism
Endothelium, Vascular/*metabolism
Gene Knockdown Techniques
Hindlimb/blood supply
Ischemia/genetics/metabolism
Mice
Mice, Knockout
Neovascularization, Physiologic/*physiology
AdipoR1
AdipoR2
Adiponectin
Angiogenesis
Ischemia
Peripheral Vascular Disease
Skeletal Muscle
T-cadherin
Vascular Biology
要旨:
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.
