title: Thrombin and exercise similarly influence expression of cell cycle genes in cultured putative endothelial progenitor cells.
abstract: Acute exercise and exercise training may influence putative endothelial progenitor cell (EPC) number and colony forming units (CFU-ECs), although the mechanisms remain unclear. This study examined the effects of in vitro thrombin supplementation and acute exercise on CFU-EC gene expression, associated with cellular proliferation and differentiation. The effect of habitual physical activity was evaluated through analysis of EPCs from chronically high- and low-active men. Participants were healthy high- and low-active men (n=23), aged 55-80 yr. Circulating CD34+/VEGFR2+ number, CFU-ECs, plasma prothrombin fragment (F1+2), and thrombin-antithrombin III were measured at rest and after 30 min of exercise. Gene expression of cyclin A2, cyclin D1, p27, VE-cadherin, and VEGFR2 was assessed in postexercise CFU-ECs and resting CFU-ECs treated with 0, 1, 5, or 10 U/ml of thrombin. Outcomes were compared between high- and low-active participants. F1+2 and thrombin-antithrombin III, but not CD34+/VEGFR2+ number and CFU-ECs, increased with exercise. Exercise-induced changes in F1+2 correlated with changes in CD34+/VEGFR2+ number in both groups. Thrombin treatments and acute exercise increased cyclin A2 and cyclin D1 expression and decreased p27 expression. One unit per milliliter thrombin increased VEGFR2 and VE-cadherin expression, whereas 5 U/ml, 10 U/ml, and acute exercise did not elicit any changes. An exercise training effect was observed with greater decreases in p27 expression with 5 and 10 U/ml thrombin and greater increases in VEGFR2 and VE-cadherin expression with 1 U/ml thrombin in high-active men. Exercise-induced changes in putative EPC gene expression are associated with thrombin production and may be modulated by long-term exercise training.
authors.affiliation: Department of Kinesiology, University of Maryland College Park School of Public Health, College Park, MD 20742-2611, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lockard
authors.forename: Sarah
authors.initials: S
authors.lastname: Witkowski
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Jenkins
authors.forename: Espen E
authors.initials: EE
authors.lastname: Spangenburg
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Obisesan
authors.forename: James M
authors.initials: JM
authors.lastname: Hagberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D005082:Physical Exertion / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D013917:Thrombin / Q000008:administration & dosage*
chemical_list: D018797:Cell Cycle Proteins; D013917:Thrombin