Differences in the reaction of hyperlipidemia on different endothelial progenitor cells based on sex

Xiaoqing Zhuo; Haoran Bu; Ke Hu; Zhihua Si; Liming Chen; Yong Chen; Le Yang; Yufan Jiang; Yixin Xu; Peng Zhao; Xiaochun Ma; Shufei Tao; Qingyi Zhu; Lianqun Cui; Haihui Sun; Yuqi Cui

doi:10.3892/br.2021.1440

Differences in the reaction of hyperlipidemia on different endothelial progenitor cells based on sex

Biomed Rep. 2021 Aug;15(2):64. doi: 10.3892/br.2021.1440. Epub 2021 Jun 7.

Authors

Xiaoqing Zhuo^{1

2}, Haoran Bu³, Ke Hu⁴, Zhihua Si⁵, Liming Chen^{1

6}, Yong Chen³, Le Yang^{1

6}, Yufan Jiang^{1

6}, Yixin Xu^{1

6}, Peng Zhao^{1

6}, Xiaochun Ma⁷, Shufei Tao⁸, Qingyi Zhu⁹, Lianqun Cui^{1

6}, Haihui Sun^{1

6}, Yuqi Cui^{1

6}

Affiliations

¹ Department of Cardiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.
² Department of Cardiology, Shandong Second Provincial General Hospital, Shandong University, Jinan, Shandong 250118, P.R. China.
³ Department of Emergency, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China.
⁴ Department of Emergency, Qianfoshan Hospital, Shandong First Medical University, Jinan, Shandong 250014, P.R. China.
⁵ Department of Neurology, Qianfoshan Hospital, Shandong First Medical University, Jinan, Shandong 250014, P.R. China.
⁶ Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China.
⁷ Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China.
⁸ Ross University School of Medicine, Barbados 60515, Barbados.
⁹ Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Abstract

The sex of a patient can affect the outcomes of several cardiovascular diseases, and men generally tend to experience earlier episodes of cardiovascular diseases compared with women. The progression of atherosclerosis during hyperlipidemia can be induced by reactive oxygen species (ROS) and oxidized-low-density lipoprotein (ox-LDL). By contrast, bone marrow (BM)-derived endothelial progenitor cells (EPCs) have been reported to serve a protective role against atherosclerosis. The aim of the present was to compare the effects of sex under conditions of hyperlipidemia on different populations of EPCs, and to identify the potential underlying mechanisms. EPC numbers and ROS levels in the blood and BM were measured using fluorescence activated cell sorting in male and female LDL receptor knock-out C57BL/6 mice maintained on a high-fat diet for 6 months, and in male and female wild type C57BL/6 mice following ox-LDL injection for 3 days. Female hyperlipidemic mice exhibited lower levels of plasma lipids, atherosclerotic plaque formation, intracellular EPC ROS formation and inflammatory cytokine levels. Furthermore, BM CD34⁺/ fetal liver kinase-1 (Flk-1⁺), CD34⁺/CD133⁺ and stem cell antigen-1⁺/Flk-1⁺, as well as all circulating EPCs, were maintained at higher levels in female hyperlipidemic mice. In addition, similar changes with regards to BM CD34⁺/Flk-1⁺, CD34⁺/CD133⁺, c-Kit⁺/CD31⁺ and circulating CD34⁺/Flk1⁺ and CD34⁺/CD133⁺ EPCs were observed in female mice following ox-LDL treatment. These sustained higher levels of BM and circulating EPCs in female mice with hyperlipidemia may be associated with reduced levels of ox-LDL as a result of reduced intracellular ROS formation in EPCs and decreased inflammatory cytokine production.

Keywords: endothelial progenitor cells; hyperlipidemia; oxidized low-density lipoprotein; reactive oxygen species; sex.

Grants and funding

Funding: This work was supported by The National Nature Science Foundation of China (grant nos. 81600222 and 81800255), Young experts of Taishan Scholar Program of Shandong Province (grant no. tsqn201812142), Academic Promotion Programme of Shandong First Medical University (grant nos. 2019RC017), The Natural Science Foundation of Shandong Province (grant nos. ZR2016HM22 and ZR2018BH002) and Clinical Medical Science and Technology Innovation Development Plan Project of Jinan in China (grant nos. 201704106).