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World J Diabetes. Nov 15, 2022; 13(11): 926-939
Published online Nov 15, 2022. doi: 10.4239/wjd.v13.i11.926
Advances in neovascularization after diabetic ischemia
Yue Cai, Guang-Yao Zang, Yan Huang, Zhen Sun, Li-Li Zhang, Yong-Jiang Qian, Wei Yuan, Zhong-Qun Wang
Yue Cai, Guang-Yao Zang, Zhen Sun, Li-Li Zhang, Yong-Jiang Qian, Wei Yuan, Zhong-Qun Wang, Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
Yan Huang, Department of Ophthalmology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
Author contributions: Cai Y, Zang GY, Huang Y and Sun Z designed, collected and interpreted data and drafted, revised and approved the manuscript; Zhang LL, Qian YJ, Yuan W and Wang ZQ interpreted data and drafted, revised and approved the manuscript.
Supported by the National Natural Science Foundation of China, No. 82070455; the Related Foundation of Jiangsu Province, No. BK20201225; the Medical Innovation Team Project of Jiangsu Province, No. CXTDA2017010; and the Postgraduate Research and Practice Innovation Program of Jiangsu Province, No. KYCX20_3051.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhong-Qun Wang, PhD, Professor, Researcher, Department of Cardiology, Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Jingkou District, Zhenjiang 212000, Jiangsu Province, China. wangtsmc@126.com
Received: August 5, 2022
Peer-review started: August 5, 2022
First decision: August 20, 2022
Revised: September 9, 2022
Accepted: November 2, 2022
Article in press: November 2, 2022
Published online: November 15, 2022
Processing time: 98 Days and 6.8 Hours
Abstract

With the high incidence of diabetes around the world, ischemic complications cause a serious influence on people’s production and living. Neovascularization plays a significant role in its development. Therefore, neovascularization after diabetic ischemia has aroused attention and has become a hot spot in recent years. Neovascularization is divided into angiogenesis represented by atherosclerosis and arteriogenesis characterized by coronary collateral circulation. When mononuclear macrophages successively migrate to the ischemia anoxic zone after ischemia or hypoxia, they induce the secretion of cytokines, such as vascular endothelial growth factor and hypoxia-inducible factor, activate signaling pathways such as classic Wnt and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathways, trigger oxidative stress response, activate endothelial progenitor cells or enter the glycolysis or lactic acid process and promote the formation of new blood vessels, remodeling them into mature blood vessels and restoring blood supply. However, the hypoglycemic condition has different impacts on neovascularization. Consequently, this review aimed to introduce the mechanisms of neovascularization after diabetic ischemia, increase our un-derstanding of diabetic ischemic complications and their therapies and provide more treatment options for clinical practice and effectively relieve patients’ pain. It is believed that in the near future, neovascularization will bring more benefits and hope to patients with diabetes.

Keywords: Diabetes mellitus; Angiogenesis; Arteriogenesis; Ischemia; Hypoxia

Core Tip: This review aimed to give an overview of neovascularization in patients with diabetes. First, we introduced the basic concepts and influencing factors of neovascularization, including angiogenesis and arteriogenesis. Second, the mechanisms regarding cytokines, classical and novel signaling pathways, glycolysis and lactic acid process and so on described in detail. Then, the neovascularization after diabetic ischemia was further described in combination with the complications of diabetes, such as diabetic atherosclerosis, diabetic retinopathy, diabetic nephropathy and diabetic foot ulcer. Last but not least, the treatment plans listed, with advantages and disadvantages, that may offer more treatment options.