Adiponectin promotes the migration of circulating angiogenic cells through p38-mediated induction of the CXCR4 receptor.
OBJECTIVE
Adiponectin (adipo) and exercise training (ET) contribute to the maintenance of a normal vascular tone by influencing vascular NO bioavailability and concentration and function of circulating angiogenic cells (CAC). The molecular mechanisms are only partially understood. Aim of the present study was to elucidate the effects of adipo on CAC migration and the underlying signaling pathways. Furthermore, the impact of ET on adiponectin-mediated CAC migration was investigated.


RESULTS
CACs were isolated from peripheral blood and exposed to different adipo concentrations. Adipo (5μg/ml) enhanced the ability of CACs to migrate following an SDF-1 gradient by 345%. This was associated with a significant increase in CXCR4 expression on the surface of CACs as compared to control (10.1 ± 1.5 vs. 33.2 ± 4.5% CXCR4 positive cells, p<0.05). Adiponectin-induced CAC migration and CXCR4-upregulation were mediated through adipo-receptor 1 (AdipoR1) and blocked by an inhibitor of PI3-kinase, p38MAP kinase and NFκb. Adipo-stimulated migration of CACs, CXCR4 expression and p38MAPK-activation is impaired in patients with coronary artery disease (CAD). ET over 4 weeks partially corrects adiponectin-stimulated CAC migration and CXCR4 expression in patients with CAD (n=10). No change was observed in the control group (n=10).


CONCLUSIONS
Adipo improves the migratory capacity of CACs in response to SDF1, partially through an upregulation of CXCR4. This is mediated through a pathway that involves binding of adipo to the AdipoR1 and subsequent PI3kinase/p38MAPK/ NFκb activation. In addition ET corrects the adiponectin responsiveness of CACs, and thereby might promote endogenous repair of damaged endothelium.
Department of Internal Medicine/Cardiology, University Leipzig, Heart Center, Leipzig, Germany.
Volker
V
Adams
John T
JT
Heiker
Robert
R
Höllriegel
Ephraim B
EB
Beck
Felix J
FJ
Woitek
Sandra
S
Erbs
Matthias
M
Blüher
Michael
M
Stumvoll
Annette G
AG
Beck-Sickinger
Gerhard
G
Schuler
Axel
A
Linke
D052242:Adiponectin / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D000368:Aged; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005080:Exercise Test / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D052242:Adiponectin; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D048051:p38 Mitogen-Activated Protein Kinases