Research Paper Volume 14, Issue 19 pp 7877—7889

Hyperlipidemia attenuates the mobilization of endothelial progenitor cells induced by acute myocardial ischemia via VEGF/eNOS/NO/MMP-9 pathway

Jidong Zhou1, *, , Hang Li1,3, *, , Liying Xun2, , Lei Wang1, , Qitao Zhao2, ,

  • 1 School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
  • 2 School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
  • 3 R&D Department, Hubei Minkang Pharmaceutical Group Co. Ltd., Wuhan 430040, China
* Equal contribution

Received: November 24, 2021       Accepted: September 17, 2022       Published: October 3, 2022
How to Cite

Copyright: © 2022 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


This study aims to explore the role of hyperlipidemia in the mobilization of bone marrow (BM) endothelial progenitor cells (EPCs) induced by acute myocardial ischemia (AMI). To establish the hyperlipidemia complicated with AMI (HL-AMI) model, SD rats were intragastrically administered the high-fat emulsion for 4 weeks. Then their left anterior descending arteries were ligated. Rats in each group were randomly subdivided into seven subgroups. During 1st ~ 7th day following AMI modeling, rats in 1st ~ 7th subgroups were selected to be phlebotomized from their celiac artery after being anesthetized by pentobarbitone in turn. The quantity of circulating EPCs (CEPCs) was detected by flow cytometry, the expression of VEGF, eNOS, NO, MMP-9 in myocardial tissue was analyzed by western blot, and their plasma level was assayed by ELISA. Dynamic curves were plotted using these data. Within 7 days following AMI, compared with the AMI rats, in the HL-AMI rats, the myocardial infarct size, the plasma activity of CK, CK-MB, and the collagen deposition all remained at the higher levels; meanwhile, these rats showed more significant decreases in the count of CEPCs, the plasma level of VEGF etc., and their expression in myocardial tissue (P < 0.05 or P < 0.01). Our study showed that hyperlipidemia may attenuate the mobilization of BM EPCs induced by AMI via VEGF/eNOS/NO/MMP-9 signal pathway, which might partly account for hyperlipidemia hampering the repairs of AMI-induced cardiac injury.


EPCs: Endothelial progenitor cells; AMI: Acute myocardial ischemia; HL: Hyperlipidemia; HL-AMI: Hyperlipidemia complicated with acute myocardial ischemia; VEGF: Vascular endothelial growth factor; eNOS: Endothelial nitric oxide syntheses; NO: Nitric oxide; MMP-9: Matrix metalloproteinase 9; CVDs: Cardiovascular diseases; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; TG: Total triglyceride; TC: Total cholesterol; HFE: High-fat emulsion; FCM: Flow cytometry analysis; Kit: Stem cell factor receptor.