Alpha-2-macroglobulin as a Promising Biological Marker of Endothelial Function

Aims: Alpha-2-macroglobulin (alpha(2)MG) is thought to be associated with inflammatory reactions and procoagulant properties that might cause ischemic stroke. Endothelial dysfunction plays an important role in atherosclerosis development and in the occurrence of cardiovascular events. In this study, we investigated whether serum alpha(2)MG levels, endothelial function, and endothelial progenitor cell (EPC) number were associated in patients with chronic stroke or cardiovascular risk factors. Methods: Patients with a history of stroke or any established cardiovascular risk factors were enrolled in this study (n = 102; 69 men, 70.1 +/- 9.2 years). Endothelial function was assessed by flow-mediated dilation (FMD). EPC numbers (CD34+/CD133+) were measured using flow cytometry (n = 91). Serum alpha(2)MG levels were measured by nephelometry. Results: Patients in the highest tertile of serum alpha(2)MG levels were older (P = 0.019) and more frequently exhibited dyslipidemia (P = 0.021). Univariate-regression analysis revealed that increased alpha(2)MG levels were negatively associated with FMD values (r = -0.25; P = 0.010), whereas increased EPC numbers were positively associated (r = 0.21; P = 0.044). Multivariate-regression analysis adjusted for male gender, hypertension, and severe white-matter lesions showed that serum alpha(2)MG levels were independently associated with FMD values (standardized partial regression coefficient [beta] -0.185; P = 0.033), although not significantly associated with EPC numbers. Conclusion: Serum alpha(2)MG levels might reflect endothelial dysfunction evaluated by FMD in patients with chronic stroke or cardiovascular risk factors.