Extracellular vesicles derived from microRNA-150-5p-overexpressing mesenchymal stem cells protect rat hearts against ischemia/reperfusion

Abstract

An intriguing area of research has demonstrated the ability of extracellular vesicles (EVs) as biological vehicles for microRNAs (miRNAs) transfer. Mesenchymal stem cells (MSCs) produce large amounts of EVs. Rat models of ischemia/reperfusion (I/R) were established to explore the expression profile of thioredoxin-interacting protein (TXNIP), which was then knocked-down to investigate its effects on myocardial remodeling, followed by detection on myocardial infarction size (MIS), myocardial collagen volume fraction (CVF) and cardiomyocyte apoptosis. MSCs-derived EVs carrying miR-150-5p were cultured with neonatal cardiomyocytes under hypoxia/hypoglycemia condition for in vitro exploration and intramyocardially injected into I/R rats for in vivo exploration. I/R-induced rats presented higher TXNIP levels and lower miR-150-5p levels, along with increased cardiomyocyte apoptosis. miR-150-5p in MSCs was transferred through EVs to cardiomyocytes, leading to suppressed myocardial remodeling, as reflected by smaller MIS and CVF and suppressed cardiomyocyte apoptosis. I/R-treated rats injected with MSCs-derived EVs containing miR-150-5p showed a reduction in myocardial remodeling associated with the downregulation of TXNIP, which may be clinically applicable for treatment of I/R.

Decreased MicroRNA-150 Exacerbates Neuronal Apoptosis in the Diabetic Retina

“…There is local hypoxia in the diabetic retina, and apoptosis of photoreceptors occurs shortly after the onset of diabetes and may contribute to neural dysfunction and vascular degeneration [ 13 , 16 ]. Inhibition of miR-150 is known to promote apoptosis [ 20 , 39 ], while overexpressing miR-150 can reduce the apoptosis of cells under hypoxia/ischemia conditions [ 21 , 40 ]. However, some cancer or endothelial cells with miR-150 overexpression have increased apoptosis under different treatments [ 41 , 42 ].…”

miR-4732-3p in Extracellular Vesicles From Mesenchymal Stromal Cells Is Cardioprotective During Myocardial Ischemia

“…For instance, intramyocardial infusion of bone marrow-derived EVs overexpressing miR-486-5p from non-human primates was demonstrated to recover cardiac function after myocardial infarction in murine and non-human primates ( Li et al, 2021 ). Similarly, delivery of MSC-derived EVs containing miR-150-5p attenuated adverse myocardial remodeling in a rat model of I/R ( Ou et al, 2020 ). Likewise, MSC-EV-derived miR-21a-5p induced cardioprotection in mice after I/R injury ( Luther et al, 2018 ), and adenovirus delivery of miR-148a prevented ventricular remodeling in mice subjected to pressure-overload ( Raso et al, 2019 ).…”

Exosomal microRNA-150-5p from bone marrow mesenchymal stromal cells mitigates cerebral ischemia/reperfusion injury via targeting B-cell translocation gene 2

“…Concretely, miR-150-5p also exhibits low level in rats with myocardial I/R injury, and the extracellular vesicles derived from miR-150-5p effectively suppress the cardiomyocyte apoptosis and myocardial remodeling, thus to favor the treatment of I/R [15]. In addition, it has been veri ed the exosomes from BMSCs can attenuate renal I/R injury [10].…”

“…Belonging to miRNA, miR-150 has been revealed to reduce vascular density of infarct border zone in middle cerebral artery occlusion (MCAO) rats and constrain the growth of brain microvascular endothelial cells [14]. In addition, Ou et al have unearthed that miR-150-5p is depleted in I/R rats, while the enrichment of miR-150-5p can repress the cardiomyocyte apoptosis in I/R rats [15]. Furthermore, the bioinformatic website predicted there was a binding relationship between miR-150-5p and B-cell translocation gene 2 (BTG2).…”