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Protection from Diabetes‐Induced Endothelial Progenitor Cell Dysfunction by ACE2/Angiotensin‐(1‐7)/Mas Receptor Axis
Author(s) -
Jarajapu Yagna Prasada Rao,
Bhatwadekar Ashay Dilip,
Caballero Sergio,
Shenoy Vinayak,
Nikinova Elena,
Tanis Keith,
Stone David,
Kent David,
Reinhold Medina,
Stitt Alan,
Thut Catherine,
Finney Eva,
Katovich Michael,
McGorray Sue,
Raizada Mohan K,
Grant Maria B
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.826.5
We tested the hypothesis that ACE2/Angiotensin (Ang)‐(1‐7)/Mas receptor axis confers protection in endothelial progenitor cells (EPCs) in diabetes. Peripheral blood lin‐CD45midCD34+ cells from nondiabetic subjects and diabetic patients were studied. ACE2 expression was lower, Mas receptor expression was unaltered and ACE2 activators, xanthenone (XNT) and diminazine aceturate (DIZE), were less effective in inducing migration in diabetic EPCs compared to nondiabetic. However, Ang‐(1‐7) stimulated migratory response in nondiabetic and restored migration in diabetic EPCs in a Mas receptor‐dependent manner. In diabetic EPCs, Ang‐(1‐7) pretreatment decreased NADPH oxidase activity and increased SDF‐mediated NO generation/cGMP production. Survival and proliferation of diabetic EPCs was enhanced by Ang‐(1‐7) activation of Mas receptor/PI3K/Akt pathway. Ang‐(1‐7) overexpression by lentiviral vector‐mediated gene modification restored vasoreparative function in diabetic EPCs in a mouse model of retinal ischemia/reperfusion injury. Microarray analysis revealed higher expressions of ACE2 and Mas receptor in EPCs from a unique population of diabetics (for >40years; Hb‐A1c 9–11%) without macro or microvascular complications (MVC) compared to those from diabetics with MVC. This study suggests that activation of the ACE2/Ang‐(1‐7)\Mas receptor pathway confers protection in diabetic EPCs.