Diabetes mellitus impairs CD133+ progenitor cell function after myocardial infarction

• Published in: Journal of internal medicine 2009-02, Vol.265 (2), p.238-249
• Main Authors: Vöö, S., Dunaeva, M., Eggermann, J., Stadler, N., Waltenberger, J.
• Format: Article
• Language: English
• Subjects: AC133 Antigen; acute myocardial infarction; Aged; Antigens, CD; Biological and medical sciences; Biomarkers; CD133; Chemotaxis - physiology; coronary heart disease; diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - blood; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Flow Cytometry; General aspects; Glycoproteins; Humans; Male; Medical sciences; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - pathology; Peptides; Pilot Projects; progenitor cells; Prospective Studies; Stem Cells - physiology; Vascular Endothelial Growth Factor Receptor-1 - blood
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/j.1365-2796.2008.02011.x

. 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.