Functional effects of adiponectin on endothelial progenitor cells.
Adiponectin is an adipokine whose plasma levels are inversely correlated to metabolic syndrome components. Adiponectin protects against atherosclerosis and decreases risks in myocardial infarction. Endothelial progenitor cells (EPCs) are a heterogeneous population of circulating cells involved in vascular repair and neovascularization. EPCs number is reduced in patients with cardiovascular disease. We hypothesize that the positive effects of adiponectin against atherosclerosis are explained in part by its interactions with EPCs. Cells were obtained from healthy volunteers' blood by mononuclear cell isolation and plating on collagen-coated dishes. Three sub-populations of EPCs were identified and characterized using flow cytometry. EPCs' expression of adiponectin receptors, AdipoR1, and AdipoR2 was evaluated by quantitative PCR. The effects of recombinant adiponectin on EPCs' susceptibility to apoptosis were assessed. Finally, expression of neutrophil elastase by EPCs and activity of this enzyme on adiponectin processing were assessed. Quantitative PCR analysis of EPCs mRNAs showed that AdipoR1 mRNA is expressed at higher levels than AdipoR2. Expression of AdipoR1 protein was confirmed by western blot. Adiponectin significantly increased survival of two sub-populations of EPCs in conditions of serum deprivation. Such effect could not be demonstrated in the third EPCs sub-population. We also demonstrated that EPCs, particularly one sub-population, express neutrophil elastase. Neutrophil elastase activity was confirmed in EPCs' conditioned media. Adiponectin protects some EPCs sub-populations against apoptosis and therefore could modulate EPCs ability to induce repair of vascular damage. Neutrophil elastase activity of EPCs could locally modulate adiponectin activity by its involvement in the generation of the globular form of adiponectin.
Lavoie
Véronique
V
Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.
Kernaleguen
Anne-Elen
AE
Charron
Guy
G
Farhat
Nada
N
Cossette
Mariève
M
Mamarbachi
Aida M
AM
Allen
Bruce G
BG
Rhéaume
Eric
E
Tardif
Jean-Claude
JC
D052242:Adiponectin / Q000097:blood* / Q000494:pharmacology*; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D001774:Blood Chemical Analysis / Q000379:methods; D015153:Blotting, Western; D002469:Cell Separation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D054419:Receptors, Adiponectin / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D019272:Leukocyte Elastase