@article{APS10738,
author = {Cheng Peng and Li-jun Yang and Chuan Zhang and Yu Jiang and Liu-wen-xin Shang and Jia-bei He and Zhen-wei Zhou and Xia Tao and Lu Tie and Alex F. Chen and He-hui Xie},
title = {Low-dose nifedipine rescues impaired endothelial progenitor cell-mediated angiogenesis in diabetic mice},
journal = {Acta Pharmacologica Sinica},
volume = {44},
number = {1},
year = {2022},
keywords = {},
abstract = {It is of great clinical significance to develop potential novel strategies to prevent diabetic cardiovascular complications. Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic vascular complications. In the present study we evaluated whether low-dose nifedipine could rescue impaired EPC-mediated angiogenesis and prevent cardiovascular complications in diabetic mice. Diabetes was induced in mice by five consecutive injections of streptozotocin (STZ, 60 mg·kg−1·d−1, i.p.). Diabetic mice were treated with low-dose nifedipine (1.5 mg·kg−1·d−1, i.g.) for six weeks. Then, circulating EPCs in the peripheral blood were quantified, and bone marrow-derived EPCs (BM-EPCs) were prepared. We showed that administration of low-dose nifedipine significantly increased circulating EPCs, improved BM-EPCs function, promoted angiogenesis, and reduced the cerebral ischemic injury in diabetic mice. Furthermore, we found that low-dose nifedipine significantly increased endothelial nitric oxide synthase (eNOS) expression and intracellular NO levels, and decreased the levels of intracellular O .− and thrombospondin-1/2 (TSP-1/2, a potent 2 angiogenesis inhibitor) in BM-EPCs of diabetic mice. In cultured BM-EPCs, co-treatment with nifedipine (0.1, 1 μM) dose- dependently protected against high-glucose-induced impairment of migration, and suppressed high-glucose-induced TSP-1 secretion and superoxide overproduction. In mice with middle cerebral artery occlusion, intravenous injection of diabetic BM-EPCs treated with nifedipine displayed a greater ability to promote local angiogenesis and reduce cerebral ischemic injury compared to injection of diabetic BM-EPCs treated with vehicle, and the donor-derived BM-EPCs homed to the recipient ischemic brain. In conclusion, low-dose nifedipine can enhance EPCs’ angiogenic potential and protect against cerebral ischemic injury in diabetic mice. It is implied that chronic treatment with low-dose nifedipine may be a safe and economic manner to prevent ischemic diseases (including stroke) in diabetes.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10738}
}