ADSC-derived exosomes attenuate myocardial infarction injury by promoting miR-205-mediated cardiac angiogenesis

Abstract

Background Acute myocardial infarction is a major health problem and is the leading cause of death worldwide. Myocardial apoptosis induced by myocardial infarction injury is involved in the pathophysiology of heart failure. Therapeutic stem cell therapy has the potential to be an effective and favorable treatment for ischemic heart disease. Exosomes derived from stem cells have been shown to effectively repair MI injury-induced cardiomyocyte damage. However, the cardioprotective benefits of adipose tissue-derived mesenchymal stem cell (ADSC)-Exos remain unknown. This study aimed to investigate the protective effects of exosomes from ADSC on the hearts of MI-treated mice and to explore the underlying mechanisms. Methods Cellular and molecular mechanisms were investigated using cultured ADSCs. On C57BL/6J mice, we performed myocardial MI or sham operations and assessed cardiac function, fibrosis, and angiogenesis 4 weeks later. Mice were intramyocardially injected with ADSC-Exos or vehicle-treated ADSCs after 25 min following the MI operation. Results Echocardiographic experiments showed that ADSC-Exos could significantly improve left ventricular ejection fraction, whereas ADSC-Exos administration could significantly alleviate MI-induced cardiac fibrosis. Additionally, ADSC-Exos treatment has been shown to reduce cardiomyocyte apoptosis while increasing angiogenesis. Molecular experiments found that exosomes extracted from ADSCs can promote the proliferation and migration of microvascular endothelial cells, facilitate angiogenesis, and inhibit cardiomyocytes apoptosis through miRNA-205. We then transferred isolated exosomes from ADSCs into MI-induced mice and observed decreased cardiac fibrosis, increased angiogenesis, and improved cardiac function. We also observed increased apoptosis and decreased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in HMEC-1 transfected with a miRNA-205 inhibitor. Conclusion In summary, these findings show that ADSC-Exos can alleviate cardiac injury and promote cardiac function recovery in MI-treated mice via the miRNA-205 signaling pathway. ADSC-Exos containing miRNA205 have a promising therapeutic potential in MI-induced cardiac injury.

Biodegradable nano black phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve injury rat model by recruiting endogenous stem/progenitor cells

“…Recently, mesenchymal stem cells (MSCs) have been taken as the priority in SC-based treatments in regenerative medicine, as they are less immunogenic than other types of SCs (expressing low VHL) and potentiate to escape from the immune system of the recipients [ 17 – 19 ]. Notably, ADSCs, a common type of MSCs, have been widely investigated because of the edge of a wide range of tissue sources and easy extraction [ 20 ]. Hence, ADSCs were selected in this study to evaluate the ability of BP@SDF1-α to recruit SCs.…”

Basic Pathogenic Mechanisms and Epigenetic Players Promoted by Extracellular Vesicles in Vascular Damage

“…Molecular experiments demonstrated that ADSCs-derived exosomes can promote microvascular ECs proliferation and migration and inhibit cardiomyocytes apoptosis through miRNA-205. This assumption was confirmed via the transfection of ADSC-derived exosomes into MI-induced mice and observing a decrease in cardiac fibrosis, an increase in angiogenesis, and an improvement of cardiac function [ 77 ]. Cardiac fibroblast-derived EVs modulate cardiac remodeling, favoring intercellular communication between cardiomyocytes (CM) and cardiac fibroblasts [ 78 , 79 ].…”

“…Nowadays, it is known that, in the cardiovascular system, EVs also play important epigenetic-indirect roles in the acute post-myocardial infarction (MI) damage and repair mechanisms inducing myocardial remodeling and cardiac regeneration [ 76 ]. Recently, echocardiographic experiments had shown that exosomes derived from the mesenchymal stem cell of adipose tissue (ADSC) could improve left ventricular ejection fraction, whereas their administration could significantly alleviate MI-induced cardiac fibrosis [ 77 ]. Additionally, ADSC-exosomes treatment has been shown to reduce cardiomyocyte apoptosis, increasing angiogenesis.…”

Engineered exosomes and composite biomaterials for tissue regeneration

“…Additionally, ADSC-Exos containing miRNA-205 promoted angiogenesis. This study provides the primary evidence for the use of ADSC-Exos in the clinical treatment of MI 100 .…”