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

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• 作者：Yossi Issan^a ; Edith Hochhauser^a ; Austin Guo^d ; Katherine H. Gotlinger^d ; Ran Kornowski^b ; Dorit Leshem-Lev^a ; Eli Lev^b ; Eyal Porat^c ; Eitan Snir^c ; Carl I. Thompson^e ; Nader G. Abraham^f ; Michal Laniado-Schwartzman^d ; ^{michal_schwartzman@nymc.edu}
• 关键词：Endothelial progenitor cell (EPC) ; Coronary artery disease (CAD)
• 刊名：Prostaglandins and Other Lipid Mediators
• 出版年：2013
• 出版时间：January-March, 2013
• 年：2013
• 卷：100-101
• 期：Complete
• 页码：15-21
• 全文大小：319 K

文摘

Background

Circulating 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.

Results

Lipidomic analysis revealed a diabetes-specific increase (p < 0.05) in inflammatory and angiogenic eicosanoids including the 5-lipoxygenase-derived LTB₄ (4.11 ¡À 1.17 vs. 0.96 ¡À 0.27 ng/ml), the lipoxygenase/CYP-derived 12-HETE (117.08 ¡À 35.05 vs. 24.34 ¡À 10.03 ng/ml), 12-HETrE (17.56 ¡À 4.43 vs. 4.15 ¡À 2.07 ng/ml), and the CYP-derived 20-HETE (0.32 ¡À 0.04 vs. 0.06 ¡À 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.

Conclusion

This 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.