Effects Of Altitude On The Number Of Peripheral Blood Circulating Endothelial Progenitor Cells And Function Of Monocytes In Patients With Type 2 Diabetes

Object:With the development of economy and society, transition of diet and living style, the incidence of diabetes increased year by year, and diabetic vascular complications has become the main reason of death and disability. Circulating endothelial progenitor cells (EPCs) is a subpopulation of progenitor cells present in the peripheral blood, which have the capacity to proliferation and to differentiate into mature endothelial cells. Studies have shown that EPCs involved in endothelial repair and angiogenesis, it can repair damaged vessel endothelial under physiological and pathological conditions, and played an important role in the maintenance of vascular endothelial integrity. Using ficoll density gradient centrifugation can obtain Mononuclear cells, which can be induced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor and attached to pre-coated fibronectin to promote cells differentiate into EPCs. Studies have shown that peripheral blood EPCs of patients with diabetes decreased and dysfunction, while monocytes and EPCs transplantation plays an important role in the treatment of diabetic vascular complications. EPCs achieve its function of repairing damaged blood vessels and promoting angiogenesis by the mediation of various factors, hypoxic-ischemic of injury site can stimulate hypoxia-inducible factor 1α (HIF-1α) expression, which can activate its downstream genes such as stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGF), etc., to promote EPCs mobiling and homing to the site of injury to repair damaged blood vessels and promote blood vessel regeneration. Compare to plain resident with type 2 diabetes, if there is any difference on the number of EPCs and function of mononuclear of diabetic patients come from plateau where is perennial hypobaric and hypoxia. Therefore, this article aims to analyze the influences of elevation on EPCs number and mononuclear functiont of ype 2 diabetes patients, thus providing some messages for the treatment of patients with type 2 diabetic vascular complications who come from high-altitude areas.Method:1. Effcet of altitude on the number of peripheral endothelial progenitor cells. Samples consist of Chinese Han above 40 years old, who are usual residents come from Xianyang of 386 meters altitude and Lanzhou of 1520 meters altitude. The population were devided into plain group and plateau group, plain group includes 25 patients with type 2 diabetes and 20 cases of health, plateau group includes 29 type 2 diabetic patients and 20 health, between which no difference in the number of men and women.8ml peripheral blood were collectioned from each people, detect their lipids, blood glucose, glycosylated hemoglobin concentrations. Number of circulating EPCs was measured by flow cytometry.2. Effcet of altitude on the function of peripheral monocytes. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum concentration of HIF-la, SDF-1, IL-8, VEGF, and HCY. Peripheral blood mononuclear cells were obtained by density gradient centrifugation. The lever of mRNA expression of LFA-1, CXCR2, CXCR4, CXCR7 was detected by fluorescence quantitative PCR. Western blot (WesternBlot) was used to measure the protein lever of HIF-la, CXCR4, and CXCR7.Result:1. Effcet of altitude on the number of peripheral endothelial progenitor cells. Compared with healthy people, diabetes mellitus patients have higher lever of body mass index(BMI), waist-hip ratio (WHR), triglycerides, blood glucose and glycated hemoglobin; both plain and plateau type 2 diabetic patients have lower lever of circulating EPCs. Compared to plain group, both diabetes and health of plateau group have lower lever of circulating EPCs than diabetes and health come from plain.Type 2 diabetes group was divided into three:type 2 diabetes with microvascular complications group, type 2 diabetes with macrovascular complications, and type 2 diabetes without vascular complications. Compared to healthy group, the lever of circulating EPCs among these groups successively were:healthy group> type 2 diabetes without vascular complications> type 2 diabetes with microvascular complications= type 2 diabetes with macrovascular complications.2. Effcet of altitude on the function of peripheral monocytes.① Compared with the healthy group, monocytes of T2DM patients come from plateau group have lower serum concentration of HIF-1α, SDF-1, and VEGF, P<0.05, there was no difference on the concentration of IL-8; it showed no differences between plain health group and plain T2DM group on serum concentrations of HIF-la, SDF-1, VEGF, and IL-8. Compared with plain group, HIF-1αand SDF-1 concentrations of health group and diabetes group come from plateau were significantly increased, while serum concentrations of VEGF and IL-8 were significantly decreased, P<0.01. ② On the aspects of mRNA expression, CXCR2 mRNA expression of plain T2DM group significantly reduced than plain health, P<0.001, LFA-1, CXCR4 and CXCR7 mRNA expression have no difference; plateau T2DM group have significantly lower lever of CXCR2 and CXCR4 than plateau health group,P<0.001; compared with plain group, the lever of CXCR2, CXCR4 and CXCR7 mRNA expression was lower in plateau health group and plateau T2DM group, P <0.05, plateau health groups mRNA expression of CXCR2, CXCR4 and CXCR7 were 0.1,0.67 and 0.43 times than plain health group, no difference on the expression of LFA-1; plateau T2DM groups mRNA expression of CXCR2, CXCR4, CXCR7 and LFA-1 were 0.54,0.26,0.53 and 1.4 times than plain T2DM group, P<0.05. ③ On the protein lever, compared with healthy people, HIF-1 a, CXCR2, CXCR4, and CXCR7 protein lever of T2DM group were lower, when comparing to plain groups, both T2DM group and healthy group of plateau, the protein levers of CXCR2, CXCR4, and CXCR7 was down-regulated, while HIF-1 a expression was significantly up-regulated.Conclusion:T2DM patients come from plateau area have lower lever of circulating EPCs than plain T2DM patients. When it comes to the migration, and angiogenesis functions of monocyte,plateau T2DM patients were lower than plain people with T2DM, while they have better adhesion function.