Advance in mesenchymal stem cells for the treatment of cardiovascular diseases in the low- oxygen environment of plateau

doi:10.3877/cma.j.issn.2095-1221.2024.02.006

Abstract

Abstract:

The mortality rate of cardiovascular diseases is the highest among all major systems. The plateau environment is mainly characterized by hypoxia, and in the case of the heart, adapting to the hypoxic changes triggers a series of problems such as cardiomyocyte damage, ventricular remodelling, and cardiac hypoplasia. It may even induce or aggravate cardiovascular diseases. Mesenchymal stem cells (MSCs) are a novel therapeutic strategy for cell therapy. They are applied to the cardiovascular system through direct regeneration, paracrine effects, immunomodulation, microenvironmental improvement, and promotion of endogenous cardiac repair. They are highly effective in cardiovascular diseases in the low-oxygen environment of a plateau. In recent years, there have been increasing research reports on applying MSCs to prevent and treat plateau diseases in plateau areas. Now, we would like to elaborate on the effects of MSCs on the cardiovascular system in a plateau hypoxia environment, aiming to clarify the characteristics of changes in the cardiovascular system in a plateau hypoxia environment, and the mechanism and preventive and therapeutic effect of MSCs.

Key words: Highland, Hypoxia, Cardiovascular system, Mesenchymal stem cells, Exosome, HIF-1α

Guohao Liang, Qian Zhang, Yan Zhang. Advance in mesenchymal stem cells for the treatment of cardiovascular diseases in the low- oxygen environment of plateau[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(02): 107-112.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxbygxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-1221.2024.02.006

https://zhxbygxbzz.cma-cmc.com.cn/EN/Y2024/V14/I02/107

Figures/Tables 1

References 62

1	赵彩莲, 汪晓洲, 严萍. 高原病患者血压水平流行病学特征及其与糖代谢相关性分析[J]. 公共卫生与预防医学, 2022, 33(4):92-95.
2	张建起, 石蕊, 张芯, 等. 高原环境对心血管系统的影响及其防治措施[J]. 武警医学, 2022, 33(9):812-817.
3	Sriramulu S, Banerjee A, Jothimani G, et al. Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes[J]. J Basic Clin Physiol Pharmacol, 2020, 32(2):51-56.
4	Wang Y, Shen Y. Exosomal miR-455-3p from BMMSCs prevents cardiac ischemia-reperfusion injury[J]. Hum Exp Toxicol, 2022, 41:774846548. doi: 10.1177/09603271221102508.
5	Xu Y, Fan P, Liu L, et al. Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway[J]. J Zhejiang Univ Sci B, 2023, 24(2):115-129.
6	李华,李晓帆,李乃农. 间充质干细胞促进脐带血干细胞体外扩增的研究进展 [J]. 中华细胞与干细胞杂志(电子版), 2022, 12 (1): 34-38.
7	Tremblay JC, Ainslie PN. Global and country-level estimates of human population at high altitude[J]. Proc Natl Acad Sci U S A, 2021, 118(18):e2102463118. doi:10.1073/pnas.2102463118.
8	Berger MM, Luks AM. High altitude[J]. Semin Respir Crit Care Med, 2023, 44(5):681-695.
9	张秋梅. 高原低氧对机体整体的影响及适应性分析[J]. 中外医疗, 2018, 37(11):187-189.
10	毛燕, 陶磊, 庞君, 等. 低压低氧对氧化-抗氧化系统的影响[J]. 现代生物医学进展, 2015, 15(15):2981-2984.
11	Richalet JP, Hermand E, Lhuissier FJ. Cardiovascular physiology and pathophysiology at high altitude[J]. Nat Rev Cardiol, 2024, 21(2):75-88.
12	Faeh D, Gutzwiller F, Bopp M. Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland[J]. Circulation, 2009, 120(6):495-501.
13	Winkelmayer WC, Hurley MP, Liu J, et al. Altitude and the risk of cardiovascular events in incident US dialysis patients[J]. Nephrol Dial Transplant, 2012, 27(6):2411-2417.
14	Jiang M, Fan X, Wang Y, et al. Effects of hypoxia in cardiac metabolic remodeling and heart failure[J]. Exp Cell Res, 2023, 432(1):113763. doi: 10.1016/j.yexcr.2023.113763.
15	Zheng J, Chen P, Zhong J, et al. HIF-1α in myocardial ischemia-reperfusion injury (Review)[J]. Mol Med Rep, 2021, 23(5):352. doi: 10.3892/mmr.2021.11991.
16	Semenza GL. Regulation of metabolism by hypoxia-inducible factor 1[J]. Cold Spring Harb Symp Quant Biol, 2011, 76:347-353.
17	Li X, Zhang Q, Nasser MI, et al. Oxygen homeostasis and cardiovascular disease:a role for HIF?[J]. Biomed Pharmacother, 2020, 128:110338. doi: 10.1016/j.biopha.2020.110338.
18	Semenza GL. Hypoxia-inducible factor 1 and cardiovascular disease[J]. Annu Rev Physiol, 2014, 76:39-56.
19	Cornolo J, Mollard P, Brugniaux JV, et al. Autonomic control of the cardiovascular system during acclimatization to high altitude:effects of sildenafil[J]. J Appl Physiol (1985), 2004, 97(3):935-940.
20	Vogel JA, Harris CW. Cardiopulmonary responses of resting man during early exposure to high altitude[J]. J Appl Physiol, 1967, 22(6):1124-1128.
21	Han CF, Li ZY, Li TH. Roles of hypoxia-inducible factor-1α and its target genes in neonatal hypoxic pulmonary hypertension[J]. Eur Rev Med Pharmacol Sci, 2017, 21(18):4167-4180.
22	Mingji C, Onakpoya IJ, Perera R, et al. Relationship between altitude and the prevalence of hypertension in tibet: a systematic review[J]. Heart, 2015, 101(13):1054-1060.
23	陈颖, 刘洋, 王晓宇. 原发性高血压患者血清periostin、ET-1、VEGF水平变化及临床意义[J]. 中国循证心血管医学杂志, 2019, 11(4):455-457.
24	Luks AM, Hackett PH. Medical conditions and high-altitude travel[J]. N Engl J Med, 2022, 386(4):364-373.
25	Parati G, Agostoni P, Basnyat B, et al. Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: a joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine[J]. Eur Heart J, 2018, 39(17):1546-1554.
26	Richalet JP, Hermand E, Lhuissier FJ. Cardiovascular physiology and pathophysiology at high altitude[J]. Nat Rev Cardiol, 2024, 21(2):75-88.
27	王佃亮, 李燕妮. 间充质干细胞移植治疗作用机制[J]. 转化医学杂志, 2019, 8(5):257-261.
28	Naji A, Eitoku M, Favier B, et al. Biological functions of mesenchymal stem cells and clinical implications[J]. Cell Mol Life Sci, 2019, 76(17):3323-3348.
29	Eliasson P, Jönsson JI. The hematopoietic stem cell niche: low in oxygen but a nice place to be[J]. J Cell Physiol, 2010, 222(1):17-22.
30	张研, 雷胜男, 张茜, 等. 间充质干细胞及外泌体对高原脑水肿的潜在作用机制研究进展[J]. 实用临床医药杂志, 2024, 28(2):129-134.
31	Liu L, Jin X, Hu CF, et al. Exosomes derived from mesenchymal stem cells rescue myocardial ischaemia/reperfusion injury by inducing cardiomyocyte autophagy via AMPK and Akt pathways[J]. Cell Physiol Biochem, 2017, 43(1):52-68.
32	Xu W, Xu R, Li Z, et al. Hypoxia changes chemotaxis behaviour of mesenchymal stem cells via HIF-1α signalling[J]. J Cell Mol Med, 2019, 23(3):1899-1907.
33	Pulido-Escribano V, Torrecillas-Baena B, Camacho-Cardenosa M, et al. Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles[J]. World J Stem Cells, 2022, 14(7):453-472.
34	Tang Y, Zhou Y, Li HJ. Advances in mesenchymal stem cell exosomes: a review[J]. Stem Cell Res Ther, 2021, 12(1):71. doi: 10.1186/s13287-021-02138-7.
35	Sun J, Shen H, Shao L, et al. HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis[J]. Stem Cell Res Ther, 2020, 11(1):373. doi: 10.1186/s13287-020-01881-7.
36	Sun XH, Wang X, Zhang Y, et al. Exosomes of bone-marrow stromal cells inhibit cardiomyocyte apoptosis under ischemic and hypoxic conditions via miR-486-5p targeting the PTEN/PI3K/AKT signaling pathway[J]. Thromb Res, 2019, 177:23-32.
37	Wen Z, Mai Z, Zhu X, et al. Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway[J]. Stem Cell Res Ther, 2020, 11(1):36. doi: 10.1186/s13287-020-1563-8.
38	Zhang S, Liu X, Ge LL, et al. Mesenchymal stromal cell-derived exosomes improve pulmonary hypertension through inhibition of pulmonary vascular remodeling[J]. Respir Res, 2020, 21(1):71. doi: 10.1186/s12931-020-1331-4.
39	Sun W, Lv J, Guo S, et al. Cellular microenvironment: a key for tuning mesenchymal stem cell senescence[J]. Front Cell Dev Biol, 2023, 11:1323678. doi: 10.3389/fcell.2023.1323678.
40	Ni X, Ou C, Guo J, et al. Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro[J]. Int J Mol Med, 2017, 40(2):418-426.
41	Müller P, Lemcke H, David R. Stem cell therapy in heart diseases-cell types, mechanisms and improvement strategies[J]. Cell Physiol Biochem, 2018, 48(6):2607-2655.
42	Song H, Song BW, Cha MJ, et al. Modification of mesenchymal stem cells for cardiac regeneration[J]. Expert Opin Biol Ther, 2010, 10(3):309-319.
43	Tsiapalis D, O'Driscoll L. Mesenchymal stem cell derived extracellular vesicles for tissue engineering and regenerative medicine applications[J]. Cells, 2020, 9(4):991.doi: 10.3390/cells9040991.
44	Pan Y, Wu W, Jiang X, et al. Mesenchymal stem cell-derived exosomes in cardiovascular and cerebrovascular diseases:from mechanisms to therapy[J]. Biomed Pharmacother, 2023, 163:114817. doi: 10.1016/j.biopha.2023.114817.
45	Sun SJ, Wei R, Li F, et al. Mesenchymal stromal cell-derived exosomes in cardiac regeneration and repair[J]. Stem Cell Reports, 2021, 16(7):1662-1673.
46	Sid-Otmane C, Perrault LP, Ly HQ. Mesenchymal stem cell mediates cardiac repair through autocrine,paracrine and endocrine axes[J]. J Transl Med, 2020, 18(1):336. doi: 10.1186/s12967-020-02504-8.
47	Liu Y, Chen J, Liang H, et al. Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling[J]. Stem Cell Res Ther, 2022, 13(1):258.
48	Constantinou C, Miranda A, Chaves P, et al. Human pluripotent stem cell-derived cardiomyocytes as a target platform for paracrine protection by cardiac mesenchymal stromal cells[J]. Sci Rep, 2020, 10(1):13016. doi: 10.1038/s41598-020-69495-w.
49	McQuaig R, Dixit P, Yamauchi A, et al. Combination of cardiac progenitor cells from the right atrium and left ventricle exhibits synergistic paracrine effects in vitro[J]. Cell Transplant, 2020, 29:2138965032. doi: 10.1177/0963689720972328.
50	余怡. 人胎肝间充质干细胞与成人骨髓间充质干细胞的免疫调节功能的比较研究[D]. 北京:北京协和医学院, 2021.
51	Wang Y, Qi Z, Yan Z, et al. Mesenchymal stem cell immunomodulation: a novel intervention mechanism in cardiovascular disease[J]. Front Cell Dev Biol, 2021, 9:742088.doi: 10.3389/fcell.2021.742088.
52	Liu J, Gao J, Liang Z, et al. Mesenchymal stem cells and their microenvironment[J]. Stem Cell Res Ther, 2022, 13(1):429. doi: 10.1186/s13287-022-02985-y.
53	Jiang F, Zhang W, Zhou M, et al. Human amniotic mesenchymal stromal cells promote bone regeneration via activating endogenous regeneration[J]. Theranostics, 2020, 10(14):6216-6230.
54	Jia N, Shen Z, Zhao S, et al. Eleutheroside E from pre- treatment of acanthopanax senticosus (Rupr.etMaxim.) harms ameliorates high-altitude-induced heart injury by regulating NLRP3 inflammasome-mediated pyroptosis via NLRP3/caspase-1 pathway[J]. Int Immunopharmacol, 2023, 121:110423. doi: 10.1016/j.intimp.2023.110423.
55	牛佳慧, 李琳, 沈国双, 等. 高原性心脏病的研究进展[J]. 高原医学杂志, 2018, 28(3):59-64.
56	Ge RL, Helun G. Current concept of chronic mountain sickness: pulmonary hypertension-related high-altitude heart disease[J]. Wilderness Environ Med, 2001, 12(3):190-194.
57	Luna-López R, Ruiz MA, Escribano SP. Pulmonary arterial hypertension[J]. Med Clin(Barc), 2022, 158(12):622-629.
58	Sun QW, Sun Z. Stem cell therapy for pulmonary arterial hypertension: an update[J]. J Heart Lung Transplant, 2022, 41(6):692-703.
59	刘鑫源, 陈兴书, 罗勇军. 波生坦防治高原肺动脉高压相关疾病研究进展[J]. 人民军医, 2020, 63(1):79-83.
60	刘方洲, 李高元, 李相俊, 等. 高原地区青年急性心肌梗死1例报道[J]. 临床合理用药杂志, 2022, 15(12):175-178.
61	薛峰. 高海拔地区对心肌梗死患者预后影响1例分析[J]. 名医, 2020, (8):46-47.
62	Wang X, Tang Y, Liu Z, et al. The application potential and advance of mesenchymal stem cell-derived exosomes in myocardial infarction[J]. Stem Cells Int, 2021, 2021:5579904. doi: 10.1155/2021/5579904.

[1]	Chiqiu Wu, Shudong Wei, Hui Zhang, Xuqing Yan, Zuoga Meiduo, Dan Yu. Assessment of left and right ventricular morphology and function after acclimatization at different altitudes by echocardiography [J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(06): 588-593.
[2]	Ruifeng Deng, Lu Cheng, Yulin Zhou, Yuanling Liu, Wencong Jiang, Minyao Jiang, Funeng Jiang, Ming Xi. TGF-β1 induced hBMSCs exosomes to secrete miR-424-3p to promote the proliferation and migration of prostate cancer cells [J]. Chinese Journal of Endourology(Electronic Edition), 2024, 18(01): 82-89.
[3]	Zhipeng Wang, Qian Zhang, Yanhuan Huang, Yun Sun, Xiaoming Fang, Yujia Shi. Expression and clinical significance of serum exosomal hsa_circ_0018430 in lung squamous cell carcinoma [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(06): 774-778.
[4]	Shuxun Ling, Yue Tu, Siyi Liu. Visualization analysis on knowledge map of mesenchymal stem cells in the research field of chronic kidney disease [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(02): 73-82.
[5]	Juan Wang, Ye Liu, Wei Xiong, Cailei Jiang, Yan He, Qingsong Ye. A novel therapeutic mechanism for mesenchymal stem cells to alleviate oxidative stress in Alzheimer's disease [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(02): 93-106.
[6]	Wenyu Zhang, Yuxiang Huang. Research progress in large-scale cultivation of mesenchymal stem cells in vitro [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(06): 370-376.
[7]	Jia Liu, Li Fu, Yuemei Yang. Impacts of miR-138-5p on trophoblast invasion and angiogenesis by regulating the HIF-1α/Notch1 axis [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(05): 277-287.
[8]	Jiaming Fan, Ziying Yang, Zhenhui Feng, Yihuan Chen, Yutong Wang, Zhenya Shen. Analysis of differential miRNA expression related to the efficacy of stem cell transplantation in dilated cardiomyopathy [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(05): 288-298.
[9]	Jun Wu, Lixuan Chen, Yang Xiao. Analysis of dual filing research projects on stem cells in China [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(05): 304-309.
[10]	Jingxuan Shi, Yuanyuan Jiao, Jingwei Tian, Li Zhuo. Efficacy of mesenchymal stem cells-derived exosomes in the treatment of diabetic kidney disease in animals: a meta-analysis [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(02): 79-86.
[11]	Zhangning Fu, Xiaodong Geng, Yongjun Zhang, Yuping Lu, Guannan Sun, Yifan Zhang, Guangyan Cai, Xiangmei Chen, Quan Hong. Research progress on the mechanism of mesenchymal stem cells in promoting renal injury repair [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(02): 87-91.
[12]	Yifan Zhang, Xiaodong Geng, Yuwei Ji, Keying Zhang, Shupeng Lin, Guangyan Cai, Xiangmei Chen, Quan Hong. LRG1 enhanced the efficacy of mesenchymal stem cells in the treatment of acute kidney injury [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(01): 16-25.
[13]	Xinxin Hu, Xiaofan Meng, Zhaoan Guo. Research progress on the pathogenesis of hypertensive nephropathy [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(06): 339-343.
[14]	Ke Zhang, Linlin Yan, Pengfei Wang, Xiulin Zhang, Fan Zhao, Shoukui Hu. Roles of exosomal circRNA in tumour immunity and cancer immunotherapy [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(10): 1102-1108.
[15]	Ganzhe Liu, Fen Ai. MiRNA-210 improved vascular cognitive impairment in rats by inhibiting HIF-1α expression [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2023, 17(05): 489-494.

Please choose a citation manager

Content to export