TY - JOUR
T1 - Elevated level of pro-inflammatory eicosanoids and EPC dysfunction in diabetic patients with cardiac ischemia
AU - Issan, Yossi
AU - Hochhauser, Edith
AU - Guo, Austin
AU - Gotlinger, Katherine H.
AU - Kornowski, Ran
AU - Leshem-Lev, Dorit
AU - Lev, Eli
AU - Porat, Eyal
AU - Snir, Eitan
AU - Thompson, Carl I.
AU - Abraham, Nader G.
AU - Laniado-Schwartzman, Michal
N1 - Funding Information:
This study was supported in part by National Institute of Health grant HL343000 . This work was performed in partial fulfillment of the requirements for a Ph.D. degree of Yossi Issan, Sackler Faculty of Medicine, Tel Aviv University, Israel.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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 ± 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. 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.
AB - 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 ± 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. 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.
KW - Coronary artery disease (CAD)
KW - Endothelial progenitor cell (EPC)
UR - http://www.scopus.com/inward/record.url?scp=84874979531&partnerID=8YFLogxK
U2 - 10.1016/j.prostaglandins.2012.12.002
DO - 10.1016/j.prostaglandins.2012.12.002
M3 - Article
C2 - 23291334
AN - SCOPUS:84874979531
VL - 100-101
SP - 15
EP - 21
JO - Prostaglandins and Other Lipid Mediators
JF - Prostaglandins and Other Lipid Mediators
SN - 1098-8823
IS - 1
ER -
