Exercise training increases endothelial progenitor cells and decreases asymmetric dimethylarginine in peripheral arterial disease: a randomized controlled trial.

Abstract

BACKGROUND:

Supervised exercise training (SET) is recommended as initial treatment to improve walking capacity in peripheral arterial disease (PAD) patients with intermittent claudication. Various mechanisms by which SET yields beneficial effects are postulated, however data regarding its influence on angiogenesis are scarce. Thus, we designed a prospective randomized controlled trial to study the impact of SET on markers of angiogenesis and endothelial function in PAD.

METHODS:

Forty PAD patients were randomized to SET on top of best medical treatment (SET+BMT) for 6 months versus best medical treatment (BMT) only. Endothelial progenitor cells (EPC) were assessed by whole-blood flow cytometry (co-expression of CD34+ CD133+ KDR+) and cell culture assays (endothelial cell-colony forming units, circulating angiogenic cells, migration assay) at baseline, 3, 6 and 12-months after inclusion. Changes of plasma levels of asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1) and maximum walking distance were determined.

RESULTS:

EPC - measured by flow cytometric and cell culture techniques - increased significantly upon training paralleled by a significant decrease of ADMA when compared to the BMT group (p<0.05). Six months after training cessation, the beneficial effect of SET on EPC diminished, but maximum walking distance was significantly improved compared to baseline and controls (p<0.05). No significant changes were observed for VEGF and SDF-1 plasma levels in time course.

CONCLUSIONS:

SET increases circulating EPC counts and decreases ADMA levels reflecting enhanced angiogenesis and improved endothelial function, which might contribute to cardiovascular risk reduction.

• Authors: Oliver Schlager, Aura Giurgea, Othmar Schuhfried, Daniela Seidinger, Alexandra Hammer, Marion Gröger, Veronika Fialka-Moser, Michael Gschwandtner, Renate Koppensteiner, Sabine Steiner
• Journal: Atherosclerosis (Atherosclerosis) Vol. 217 Issue 1 Pg. 240-8 (Jul 2011) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 21481871 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Chemokine CXCL12
• Vascular Endothelial Growth Factor A
• N,N-dimethylarginine
• Arginine

Topics

• Aged
• Arginine (analogs & derivatives, blood)
• Cell Movement
• Chemokine CXCL12 (blood)
• Endothelial Cells (cytology)
• Exercise
• Female
• Flow Cytometry (methods)
• Humans
• Intermittent Claudication (diagnosis, therapy)
• Male
• Middle Aged
• Neovascularization, Pathologic
• Peripheral Arterial Disease (blood, therapy)
• Stem Cells (cytology)
• Time Factors
• Vascular Endothelial Growth Factor A (blood)