Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?
Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on "VEGF uncoupling with nitric oxide" and "competitive angiopoietin 1/angiopoietin 2" mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.
Beijing Key Laboratory of Diabetes Prevention and Research, Luhe Hospital, Capital Medical University, Beijing 101149, China; Department of Endocrinology, Luhe Hospital, Capital Medical University, Beijing 101149, China.
Cai-Guo
CG
Yu
Beijing Key Laboratory of Diabetes Prevention and Research, Luhe Hospital, Capital Medical University, Beijing 101149, China; Department of Endocrinology, Luhe Hospital, Capital Medical University, Beijing 101149, China.
Ning
N
Zhang
Beijing Key Laboratory of Diabetes Prevention and Research, Luhe Hospital, Capital Medical University, Beijing 101149, China; Department of Endocrinology, Luhe Hospital, Capital Medical University, Beijing 101149, China.
Sha-Sha
SS
Yuan
Beijing Key Laboratory of Diabetes Prevention and Research, Luhe Hospital, Capital Medical University, Beijing 101149, China; Department of Endocrinology, Luhe Hospital, Capital Medical University, Beijing 101149, China.
Yan
Y
Ma
Beijing Key Laboratory of Diabetes Prevention and Research, Luhe Hospital, Capital Medical University, Beijing 101149, China; Department of Endocrinology, Luhe Hospital, Capital Medical University, Beijing 101149, China.
Long-Yan
LY
Yang
Beijing Key Laboratory of Diabetes Prevention and Research, Luhe Hospital, Capital Medical University, Beijing 101149, China; Department of Endocrinology, Luhe Hospital, Capital Medical University, Beijing 101149, China.
Ying-Mei
YM
Feng
Beijing Key Laboratory of Diabetes Prevention and Research, Luhe Hospital, Capital Medical University, Beijing 101149, China; Department of Endocrinology, Luhe Hospital, Capital Medical University, Beijing 101149, China.
Dong
D
Zhao