Regulation of angiogenesis by the aging suppressor gene klotho.
Advanced age is a major risk factor of peripheral artery disease. We examined the effects of the aging-suppressor gene klotho on angiogenesis in response to ischemia by introducing ischemic hindlimb model in mice heterozygously deficient for the klotho gene and in wild type mice. Blood flow recovery as assessed by laser doppler perfusion imaging and angiogenesis as assessed by density of PECAM-1/CD31-positive positive capillaries were markedly impaired in mice heterozygously deficient for the klotho gene (both <0.05). Our findings show that the aging-suppressor gene klotho affects angiogenesis and the possibility that age-related impairment of angiogenesis might be regulated by the klotho gene. Our results present a new possibility of therapeutic angiogenesis for patients of advanced age.
Fukino
Keiko
K
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Suzuki
Toru
T
Saito
Yuichiro
Y
Shindo
Takayuki
T
Amaki
Toshihiro
T
Kurabayashi
Masahiko
M
Nagai
Ryozo
R
D000375:Aging / Q000235:genetics*; D000818:Animals; D016153:Genes, Suppressor; D005966:Glucuronidase; D006579:Heterozygote; D007511:Ischemia / Q000235:genetics; D000090265:Klotho Proteins; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics*; D013997:Time Factors
D008565:Membrane Proteins; D005966:Glucuronidase; D000090265:Klotho Proteins