Author:
Zhu Wenwu,Wang Qingjie,Zhang Jian,Sun Ling,Hong Xiu,Du Wei,Duan Rui,Jiang Jianguang,Ji Yuan,Wang Haoran,Han Bing
Abstract
Abstract
Aims
Exosomes are known as nanovesicles that are naturally secreted, playing an essential role in stem-mediated cardioprotection. This study mainly focused on investigating if exosomes derived from miR-214 overexpressing mesenchymal stem cells (MSCs) show more valid cardioprotective ability in a rat model of acute myocardial infarction (AMI) and its potential mechanisms.
Methods
Exosomes were isolated from control MSCs (Ctrl-Exo) and miR-214 overexpressing MSCs (miR-214OE-Exo) and then they were delivered to cardiomyocytes and endothelial cells in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulated genes and signal pathways by miR-214OE-Exo treatment were explored using western blot analysis and luciferase assay.
Results in vitro
, miR-214OE-Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214OE-Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214OE-Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214OE-Exo accelerated angiogenesis in peri-infarct region. Mechanistically, we identified that exosomal miR-214-3p promoted cardiac repair via targeting PTEN and activating p-AKT signal pathway.
Conclusion
Exosomes derived from miR-214 overexpressing MSCs have greatly strengthened the therapeutic efficacy for treatment of AMI by promoting cardiomyocyte survival and endothelial cell function.
Graphical abstract
Funder
the Youth medical innovation project of Xuzhou Health Commission
Science and Technology Service Network Plan
the Young Talent Development Plan of Changzhou Health Commission
the Natural Science Foundation of Jiangsu Province
the National Natural Science Foundation of China
Nanjing Universities of Chinese Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Biomedical Engineering,Biomaterials,Medicine (miscellaneous),Ceramics and Composites
Reference39 articles.
1. Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the global burden of Disease Study 2017. Lancet (London England). 2019;394(10204):1145–58.
2. Du Z, Shu Z, Li C, et al. Baoyuan decoction alleviates myocardial infarction through the regulation of metabolic dysfunction and the mitochondria-dependent caspase-9/3 pathway. Acupunct Herb Med. 2021;1(1):49–58.
3. Galiuto L, DeMaria A, Iliceto S. Microvascular damage during myocardial ischemia-reperfusion: pathophysiology, clinical implications and potential therapeutic approach evaluated by myocardial contrast echocardiography. Italian heart journal: official journal of the Italian Federation of Cardiology. 2000;1(2):108–16.
4. Hou Z, Qin X, Hu Y, et al. Longterm Exercise-Derived Exosomal miR-342-5p: a Novel Exerkine for Cardioprotection. Circul Res. 2019;124(9):1386–400.
5. Hinkel R, Ramanujam D, Kaczmarek V, et al. AntimiR-21 prevents myocardial dysfunction in a Pig Model of Ischemia/Reperfusion Injury. J Am Coll Cardiol. 2020;75(15):1788–800.
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