Diabetes mellitus impairs CD133+ progenitor cell function after myocardial infarction.
BACKGROUND
Circulating progenitor cells (PC) can positively influence the healing of ischaemic myocardium. Cardiovascular risk factors including diabetes mellitus (DM) may have a negative influence on both number and recruitment of PC. Recent evidence suggests that less differentiated CD133(+)PC contribute to myocardial healing and are promising candidates for therapy. Therefore, we investigated whether DM affects CD133(+)PC.


METHODS
CD133(+)PC were analyzed in patients following acute myocardial infarction and successful reperfusion [acute myocardial infarction (AMI, n=45) with/without non-insulin-requiring type 2 DM (T2DM)]. Stable coronary artery disease patients (CAD, n = 45) served as stable controls. Number and phenotype of CD133(+)PC were assessed by flow cytometry. CD133(+)PC chemotaxis was assessed towards vascular endothelial growth factor, an angiogenic stimulus upregulated in AMI. The expression of anti-oxidant enzymes in CD133(+)PC was detected by reverse-transcriptase PCR.


RESULTS
In non-DM patients, the number of CD133(+)PC increased on day 3 following AMI (P=0.0001). In contrast, no changes were observed in AMI patients with T2DM. Regarding the function of CD133(+)PC, an enhanced chemotactic response was observed following AMI in both non-DM (P=0.0001) and T2DM (P=0.007). However, the AMI-related functional activation was significantly weaker in diabetic patients (P=0.001). Moreover, the expression of catalase was lower in CD133(+)PC from T2DM.


CONCLUSIONS
Our results show that T2DM not only limits the abundance of CD133(+)PC following AMI, but also limits their activation. This might be explained by a lower resistance of CD133(+)PC to oxidative stress. Our data provide a possible explanation for the delayed postischaemic vascular healing and myocardial recovery in DM.
Vöö
S
S
Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
Dunaeva
M
M
Eggermann
J
J
Stadler
N
N
Waltenberger
J
J
D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD; D015415:Biomarkers; D002633:Chemotaxis / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003925:Diabetic Angiopathies / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000473:pathology; D010455:Peptides; D010865:Pilot Projects; D011446:Prospective Studies; D013234:Stem Cells / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D040281:Vascular Endothelial Growth Factor Receptor-1