title: Circulating endothelial progenitor cells and cellular membrane microparticles in db/db diabetic mouse: possible implications in cerebral ischemic damage.
abstract: For determining the implications of circulating endothelial progenitor cells (cEPCs) and cellular membrane microparticles (MPs) in diabetic stroke, levels of EPCs, EPC-MPs, and endothelium-derived MPs (EMPs) and their correlations with blood glucose concentration, cerebral microvascular density (cMVD), and ischemic damage were investigated in type 2 diabetic db/db and db/+ (wild-type control) mice. Therapeutic efficacy of EPC infusion (preincubated with MPs) was also explored. Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) surgery. Ischemic damage and cMVD were determined using histological analyses. The levels of cEPCs and MPs were determined using flow cytometric analyses. EPC generation and functions were evaluated by in vitro cell cultures. Results showed the following. 1) In db/db mice, the basal level of cEPCs was less and cMVDs were lower, but the levels of circulating EPC-MPs and EMPs were more; 2) MCAO induced a larger infarct volume and less of an increase in cEPCs in db/db mice; 3) the level of cEPCs correlated with blood glucose concentration (negatively), cMVD (positively), and ischemic damage (negatively), but the levels of EPC-MPs and EMPs correlated inversely with those parameters; 4) EPCs were reduced and dysfunctional in db/db mice, and preincubation with db/db MPs impaired EPC functions; and 5) infusion of EPCs preincubated with db/+ MPs increased the level of cEPCs and reduced ischemic damage, and these beneficial effects were reduced or lost in EPCs preincubated with db/db MPs. These data suggest that reduced cEPCs, impaired EPC generation/function, and increased production of MPs might be the mechanisms responsible for increased ischemic damage seen in db/db mice.
authors.affiliation: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio 45435, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Chen
authors.forename: Yusen
authors.initials: Y
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Jinju
authors.initials: J
authors.lastname: Wang
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000473:pathology / Q000502:physiology; D002545:Brain Ischemia / Q000097:blood / Q000209:etiology* / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000473:pathology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology* / Q000502:physiology; D006720:Homozygote; D002534:Hypoxia, Brain / Q000097:blood / Q000209:etiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012307:Risk Factors; D013234:Stem Cells / Q000473:pathology* / Q000502:physiology