Kesidou Despoina, da Costa Martins Paula A, de Windt Leon J, Brittan Mairi, Beqqali Abdelaziz, Baker Andrew Howard
Centre for Cardiovascular Science, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
Department of Molecular Genetics, Faculty of Science and Engineering, Maastricht University, Maastricht, Netherlands.
Front Physiol. 2020 Sep 25;11:579892. doi: 10.3389/fphys.2020.579892. eCollection 2020.
Cardiovascular disease (CVD) is the leading cause of mortality worldwide claiming almost 17. 9 million deaths annually. A primary cause is atherosclerosis within the coronary arteries, which restricts blood flow to the heart muscle resulting in myocardial infarction (MI) and cardiac cell death. Despite substantial progress in the management of coronary heart disease (CHD), there is still a significant number of patients developing chronic heart failure post-MI. Recent research has been focused on promoting neovascularisation post-MI with the ultimate goal being to reduce the extent of injury and improve function in the failing myocardium. Cardiac cell transplantation studies in pre-clinical models have shown improvement in cardiac function; nonetheless, poor retention of the cells has indicated a paracrine mechanism for the observed improvement. Cell communication in a paracrine manner is controlled by various mechanisms, including extracellular vesicles (EVs). EVs have emerged as novel regulators of intercellular communication, by transferring molecules able to influence molecular pathways in the recipient cell. Several studies have demonstrated the ability of EVs to stimulate angiogenesis by transferring microRNA (miRNA, miR) molecules to endothelial cells (ECs). In this review, we describe the process of neovascularisation and current developments in modulating neovascularisation in the heart using miRNAs and EV-bound miRNAs. Furthermore, we critically evaluate methods used in cell culture, EV isolation and administration.
心血管疾病(CVD)是全球主要的死亡原因,每年导致近1790万人死亡。主要原因是冠状动脉内的动脉粥样硬化,它会限制流向心肌的血液,导致心肌梗死(MI)和心肌细胞死亡。尽管在冠心病(CHD)的管理方面取得了重大进展,但仍有相当数量的患者在心肌梗死后发展为慢性心力衰竭。最近的研究集中在促进心肌梗死后的新生血管形成,最终目标是减少损伤程度并改善衰竭心肌的功能。临床前模型中的心脏细胞移植研究显示心脏功能有所改善;然而,细胞保留不佳表明观察到的改善存在旁分泌机制。旁分泌方式的细胞通讯受多种机制控制,包括细胞外囊泡(EVs)。EVs已成为细胞间通讯的新型调节因子,通过转移能够影响受体细胞分子途径的分子来实现。多项研究表明,EVs通过将微小RNA(miRNA,miR)分子转移到内皮细胞(ECs)来刺激血管生成。在本综述中,我们描述了新生血管形成的过程以及使用miRNA和与EV结合的miRNA调节心脏新生血管形成的当前进展。此外,我们批判性地评估了细胞培养、EV分离和给药中使用的方法。