Extracellular Vesicle miRNAs in the Promotion of Cardiac Neovascularisation

Abstract

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.

Predictive value of miRNA-21 on coronary restenosis after percutaneous coronary intervention in patients with coronary heart disease

“…MiRNA has been widely used in cancer and other diseases, and has been the center of attention in the field of CHD. [ 31 – 33 ] I has been proved that MiRNA-21 can promote cell proliferation and antagonize apoptosis, which affects the formation of neointima in vascular wall and participates in the pathological process of vascular stenosis. [ 34 ] The researches of miRNA-21 on ischemic heart disease is still in its infancy, and the role of restenosis after PCI is still controversial.…”

New Developments in Exosomal lncRNAs in Cardiovascular Diseases

“…In addition to cell therapy to rescue and restore cardiomyocytes, increasing research suggests that promoting the survival of cardiac endothelial cells, treating cardiac angiogenesis, and mediating the recanalization of cardiac collaterals have great therapeutic potential for the treatment of myocardial infarction. Examples include angiogenesis gene therapy (82), proangiogenic stem cell therapy (83), angiogenic ncRNA therapy (84), and exosome-and exosome-derived proangiogenic ncRNA therapy (85)(86)(87)(88). For example, a study by Ma et al showed that exosomes derived from murine BMSCs can deliver MIR132, induce tube formation in HUVECs in vitro, and promote angiogenesis in the ischemic area of the infarcted heart in mice (89).…”

Extracellular vesicles derived from mesenchymal stromal cells mediate endogenous cell growth and migration via the CXCL5 and CXCL6/CXCR2 axes and repair menisci

“…EVs lack immunogenicity; thus, they demonstrate potential as a cell-free drug for tissue regeneration in an animal model [ 15 ]. Furthermore, they have displayed therapeutic efficacy against ischemic heart disease [ 16 ] and kidney disease [ 17 ] and promoted wound healing [ 18 ] and cartilage regeneration [ 19 ]. However, the therapeutic efficacy of EVs in meniscus regeneration is uncertain.…”