Elevated level of pro-inflammatory eicosanoids and EPC dysfunction in diabetic patients with cardiac ischemia

BackgroundCirculating endothelial progenitor cells (EPCs) are recruited from the blood system to sites of ischemia and endothelial damage, where they contribute to the repair and development of blood vessels. Since numerous eicosanoids including leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) have been shown to exert potent pro-inflammatory activities, we examined their levels in chronic diabetic patients with severe cardiac ischemia in conjunction with the level and function of EPCs.ResultsLipidomic analysis revealed a diabetes-specific increase (p < 0.05) in inflammatory and angiogenic eicosanoids including the 5-lipoxygenase-derived LTB4 (4.11 ± 1.17 vs. 0.96 ± 0.27 ng/ml), the lipoxygenase/CYP-derived 12-HETE (117.08 ± 35.05 vs. 24.34 ± 10.03 ng/ml), 12-HETrE (17.56 ± 4.43 vs. 4.15 ± 2.07 ng/ml), and the CYP-derived 20-HETE (0.32 ± 0.04 vs. 0.06 ± 0.05 ng/ml) the level of which correlated with BMI (p = 0.0027). In contrast, levels of the CYP-derived EETs were not significantly (p = 0.36) different between these two groups. EPC levels and their colony-forming units were lower (p < 0.05) with a reduced viability in diabetic patients compared with non-diabetics. EPC function (colony-forming units (CFUs) and MTT assay) also negatively correlated with the circulating levels of HgA1C.ConclusionThis study demonstrates a close association between elevated levels of highly pro-inflammatory eicosonoids, diabetes and EPC dysfunction in patients with cardiac ischemia, indicating that chronic inflammation impact negatively on EPC function and angiogenic capacity in diabetes.

► The study identifies diabetic-specific increases in several known inflammatory eicosanoids in patients with CAD undergoing bypass surgery.
► The study demonstrates a significant correlation between BMI and serum levels of 20-HETE independent of diabetes.
► The study shows a significant diabetic-specific reduction in the number and function of circulating endothelial progenitor cells.
► The presence of a highly inflamed milieu in spite of ample angiogenic drive in diabetic patients may be the underlying cause of impaired EPC function.