Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse

Article

关键词: ENDOTHELIAL PROGENITOR CELLS;    NITRIC-OXIDE SYNTHASE;    GROWTH;    ISCHEMIA;    RISK;   

DOI  :  10.1161/01.CIR.0000139854.74847.99

来源: SCIE

【 摘 要 】

Background-The effects of aging on angiogenesis (vascular sprouting) and vasculogenesis (endothelial precursor cell [EPC] incorporation into vessels) are not well known. We examined whether ischemia-induced angiogenesis/vasculogenesis is altered in klotho (kl) mutant mice, an animal model of typical aging. Methods and Results-After unilateral hindlimb ischemia, laser Doppler blood-flow (LDBF) analysis revealed a decreased ischemic-normal LDBF ratio in kl mice. Tissue capillary density was also suppressed in kl mice (+/+>+/kl>kl/kl). Aortic-ring culture assay showed impaired angiogenesis in kl/kl mice, accompanied by reduced endothelium-derived nitric oxide release. Moreover, the rate of transplanted homologous bone marrow cells incorporated into capillaries in ischemic tissues (vasculogenesis) was lower in kl/kl mice than in wild-type (+/+) mice, which was associated with a decrease in the number of c-Kit(+)CD31(+) EPC-like mononuclear cells in bone marrow and in peripheral blood. Finally, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin restored the impaired neovascularization in kl/kl mice, accompanied by an increase in c-Kit(+)CD31(+) cells in bone marrow and peripheral blood, and enhanced angiogenesis in the aortic-ring culture. Conclusions-Angiogenesis and vasculogenesis are impaired in kl mutant mice, a model of typical aging. Moreover, the age-associated impairment of neovascularization might be a new target of statin therapy.

【 授权许可】

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