Cell Death and Exosomes Regulation After Myocardial Infarction and Ischemia-Reperfusion

Abstract

Cardiovascular disease (CVD) is the leading cause of death in the global population, accounting for about one-third of all deaths each year. Notably, with CVDs, myocardial damages result from myocardial infarction (MI) or cardiac arrhythmias caused by interrupted blood flow. Significantly, in the process of MI or myocardial ischemic-reperfusion (I/R) injury, both regulated and non-regulated cell death methods are involved. The critical factor for patients' prognosis is the infarct area's size, which determines the myocardial cells' survival. Cell therapy for MI has been a research hotspot in recent years; however, exosomes secreted by cells have attracted much attention following shortcomings concerning immunogens. Exosomes are extracellular vesicles containing several biologically active substances such as lipids, nucleic acids, and proteins. New evidence suggests that exosomes play a crucial role in regulating cell death after MI as exosomes of various stem cells can participate in the cell damage process after MI. Hence, in the review herein, we focused on introducing various cell-derived exosomes to reduce cell death after MI by regulating the cell death pathway to understand myocardial repair mechanisms better and provide a reference for clinical treatment.

Keywords: apoptosis; autophagy-dependent death; exosomes; ferroptosis; microRNA; myocardial infarction; myocardial protection; pyroptosis.

FIGURE 1

After MI, exosomes of different cell sources are injected around the infarction site, and exosomes can enter the damaged cardiomyocytes to reduce cardiomyocyte death. Exosomes are characterized by lipid bilayers, transmembrane and non-membrane binding proteins, and a high concentration of nucleic acids (DNA, mRNA, microRNA, and lncRNA).

FIGURE 2

The effect of exosomes derived from differently treated cells on autophagy of cardiomyocytes after MI. The miR-30a in exosomes secreted by cardiomyocytes after hypoxia is targeted to Atg7 for anti-autophagy; miR-93-5P in exosomes secreted by ADMSCs transfected with miR-93-5P targeted Atg12 for anti-autophagy; SDF1 protein secreted by BMMSCs transfected with SDF gene activates PI3K/AKT pathway to resist autophagy; miR-29c and miR-125b in exosomes derived from BMMSCs target PTEN and P53, respectively, to resist autophagy.

FIGURE 3

The effect of exosomes derived from differently treated cells on the pyrolysis of cardiomyocytes after MI. Human MSCs are transfected with LncRNA KLF3-AS1, and the secreted exosomal LncRNA KLF3-AS1 are highly expressed. LncRNA KLF3-AS1 inhibits miR-138-5p then inhibits pyroptosis; Exosomal miR-320b derived from unmodified human MSCs targets NLRP3 to inhibit cardiomyocyte pyroptosis; Exosomal miR-148a in exosomes derived from M2 macrophages inhibits TXINP expression to protect against cardiomyocyte pyroptosis.

FIGURE 4

The exosomes derived from human umbilical cord blood (MSCs) contain a significant amount of miR-23a-3p, which inhibits the expression of DMT1 after entering the cardiomyocytes, thereby reducing intracellular lipid oxidation and inhibiting the ferroptosis of cardiomyocytes.