Reduced levels of circulating endothelial progenitor cells in acute myocardial infarction patients with diabetes or pre-diabetes: accompanying the glycemic continuum

Abstract

BackgroundDiabetic patients have a significantly worse prognosis after an acute myocardial infarction (AMI) than their counterparts. Previous studies have shown that the number of circulating endothelial progenitor cells (EPCs) significantly increase early after an AMI in normoglycemic patients. However, it is well known that type 2 diabetes mellitus (DM) is associated with impaired function and reduced circulating EPCs levels. Nonetheless, few studies have analyzed EPCs response of diabetics to an AMI and the EPC response of pre-diabetic patients has not been reported yet. Therefore, we hypothesized that in the acute phase of an AMI, diabetic and pre-diabetics have lower circulating EPCs levels than patients with normal glucose metabolism. We also evaluated the possible capacity of chronic antidiabetic treatment in the recovery of EPCs response to an AMI in diabetics.MethodsOne-hundred AMI patients were prospectively enrolled in the study. Using the high-performance flow cytometer FACSCanto II, circulating EPCs (CD45dimCD34+KDR+ and CD45dimCD133+KDR+ cells) were quantified, within the first 24 hours of admission. In addition, as an indirect functional parameter, we also analyzed the fraction of EPCs coexpressing the homing marker CXCR4.ResultsWe found that in the acute phase of an AMI, diabetic patients presented significantly lower levels of circulating CD45dimCD34+KDR+ and CD45dimCD133+KDR+ EPCs by comparison with nondiabetics, with a parallel decrease in the subpopulations CXCR4+ (p < 0.001). Indeed, this study suggests that the impaired response of EPCs to an AMI is an early event in the natural history of DM, being present even in pre-diabetes. Our results, also demonstrated that numbers of all EPCs populations were inversely correlated with HbA1c (r = -0.432, p < 0.001 for CD45dimCD34+KDR+ cells). Finally, this study suggests that previous chronic insulin therapy (but not oral antidiabetic drugs) attenuate the deficient response of diabetic EPCs to an AMI.ConclusionThis study indicates that there is a progressive decrease in EPCs levels, from pre-diabetes to DM, in AMI patients. Moreover, glycemic control seems to be determinant for circulating EPCs levels presented in the acute phase of an AMI and chronic insulin therapy may probably attenuate the deficit in EPCs pool seen in diabetics.

Vistafin as an Independent Predictor for Declined Numerous of Non-Classical Endothelial Progenitor Cells in Patients with Type 2 Diabetes Mellitus

“…Glucose toxicity and lipid toxicity impair endothelial nitric oxide synthase activity as well as enhances the production of reactive oxygen species, leading to endothelial dysfunction and pro-atherogenetic alterations [32,33]. Agiopoetic EPCs were found as component of endogenous repair system that plays a pivotal role in endothelial function restore, inducing angiogenesis, and neovascularization [33].…”

“…Diabetes-induced EPC dysfunction is a critical factor in microvascular and macrovascular complications [31][32][33]. Glucose toxicity and lipid toxicity impair endothelial nitric oxide synthase activity as well as enhances the production of reactive oxygen species, leading to endothelial dysfunction and pro-atherogenetic alterations [32,33].…”

“…Decreased numerous of circulating EPCs was found a marker of impaired endothelial function and early atherosclerosis [21]. Therefore, increased production of reactive oxygen species, insulin resistance, reduced NO bioavailability have been identified as mediators of tissue injury leading to lowered EPC functionality and reduced angiogenic capacity in vivo [22][23][24]. Although decreased number and impaired functions of EPCs may associate with CV disease including atherosclerosis, the role of vistafin in regulation of angiogenic EPC subset maturation in T2DM patients without known atherosclerosis is still not fully understood.…”

Endothelial progenitor cells in diabetes complications

“…Данные механизмы объясняют неадекватную мобилизацию ЭПК из КМ в присутствии высокого уровня VEGF и SDF-1 плазмы у пациентов с СД2. Результаты следующего исследования [55] также показали, что в острой фазе ИМ у больных СД2 отмечается более низ-кий уровень циркулирующих ЭПК (CD34+KDR+CD45-и CD133+KDR+CD45-) по сравнению с больными без СД. Кроме того, в данной работе исследователи обнаружили, что у больных с преддиабетом и ИМ уровень клеток сни-жен по сравнению с группой пациентов с нормальным углеводным обменом.…”

“…со-общается, что уровень CD34+CD133+ клеток прогнозирует развитие неблагоприятных кардиоваскулярных исходов в течение двухлетнего наблюдения у больных с ОКС, пере-несших стентирование коронарных артерий [58]. В других исследованиях также было показано, что снижение цирку-лирующих ЭПК и нарушение миграционной активности клеток прогнозирует развитие неблагоприятных сердечно-сосудистых событий после перенесенного инфаркта мио-карда (ИМ) [54,55].…”