Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation

8-week-old C57BL/6J mice (n？=？27) were equally divided into group 1 (fed with 22-week control diet), group 2 (22-week high fat diet), and group 3 (14-week high fat diet, followed by 8-week control diet). Critical limb ischemia (CLI) was induced at week 20 in groups 2 and 3. The animals were sacrificed at the end of 22 weeks.Heart weight, body weight, abdominal fat weight, serum total cholesterol level, and fasting blood sugar were highest in group 2 (all p？<？0.001). The numbers of circulating EPCs (C-kit/CD31+, Sca-1/KDR？+？and CXCR4/CD34+) were lower in groups 1 and 2 than in group 3 at 18？h after CLI induction (p？<？0.03). The numbers of differentiated EPCs (C-kit/CD31+, CXCR4/CD34+ and CD133+) from adipose tissue after 14-day cultivation were also lowest in group 2 (p？<？0.001). Protein expressions of VCAM-1, oxidative index, Smad3, and TGF-β were higher, whereas the Smad1/5 and BMP-2, mitochondrial cytochrome-C SDF-1α and CXCR4 were lower in group 2 than in groups 1 and 3 (all p？<？0.02). Immunofluorescent staining of CD31+ and vWF？+？cells, the number of small vessel (<15？μm), and blood flow through Laser Doppler scanning of ischemic area were lower in group 2 compared to groups 1 and 3 on day 14 after CLI induction (all p？<？0.001).Obesity suppressed abilities of angiogenesis and recovery from CLI that were reversed by obesity control.The dramatic increase in the prevalence of obesity is mainly due to living in an environment characterized by calorie-rich foods and lack of physical activity, especially in Western countries [1]. Abundant data have demonstrated that obesity predisposes to a variety of low-grade chronic and systemic inflammatory diseases, including insulin resistance, type 2 diabetes, fatty liver diseases, osteoarthritis, atherosclerosis and its complications [2-7]. Epidemiologic studies have shown that obesity constitutes a major health threat because of its associated morbidity and mortality, especially those from cardiovascular diseases [8-10].Studi