Bone marrow mesenchymal stem cell-derived exosomes attenuate cardiac hypertrophy and fibrosis in pressure overload induc
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Bone marrow mesenchymal stem cell-derived exosomes attenuate cardiac hypertrophy and fibrosis in pressure overload induced remodeling Fu Chen 1 & Xueling Li 1 & Jinxuan Zhao 1 & Jin Geng 2 & Jun Xie 1 & Biao Xu 1 Received: 25 March 2020 / Accepted: 3 July 2020 / Editor: Tetsuji Okamoto # The Society for In Vitro Biology 2020
Abstract The multiple therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) have been verified in ischemic and reperfusion diseases. Exosomes are thought to play vital roles in MSCs-related cardioprotective effects. Recently, more and more evidences indicated that apoptosis and fibrosis were crucial pathological mechanisms in cardiac remodeling. Whether MSCs-derived exosomes could regulate cardiac hypertrophy and remodeling need to be explored. Murine BM-MSCs-derived exosomes were isolated by differential gradient centrifugation method. The transverse aortic constriction (TAC) mice model was established to promote cardiac remodeling. Cardiac function and remodeling were assessed via echocardiography and histology analysis. Myocytes apoptosis was determined by TUNEL fluorescence staining. Meanwhile, premature senescence was detected by β-galactosidase (SA-β-gal) staining. Related proteins and mRNA alternation were assessed via western blotting and quantitative reverse transcription polymerase chain reaction, respectively. MSCs-derived exosomes significantly protected myocardium against cardiac hypertrophy, attenuated myocardial apoptosis, and fibrosis and preserved heart function when pressure overload. In cultured myocytes, MSCs-derived exosomes also prevented cell hypertrophy stimulated with angiotensin II. One the other hand, exosomes promoted premature senescence of myofibroblasts vitro, indicating its anti-fibrosis effect in cardiac remodeling. Exosomes protected cardiomyocytes against pathological hypertrophy. It may provide a promising future treatment for heart failure. Keywords Mesenchymal stem cell . Exosome . Cardiac hypertrophy . Apoptosis . Senescence
Introduction In recent years, the growing prevalence of heart failure worldwide causes enormous economic cost and losses of lives. One major pathological cause of heart failure is pathological hypertrophy, which can protect the heart in a compensatory way to reduce vascular wall stress in the beginning (Hill and Olson Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11626-020-00481-2) contains supplementary material, which is available to authorized users. * Jun Xie [email protected] * Biao Xu [email protected] 1
Department of Cardiology, Drum Tower Hospital, Medical School of Nanjing University , Nanjing 210008, China
2
Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China
2008). However, sustained hypertrophy progress can result in contractile dysfunction, eventually heart failure and even sudden cardiac arrest (Barry and Townsend 2010). Over the last decades, mesenchymal stem cells (MSCs) ha
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