The Roles of Exosome-Derived microRNAs in Cardiac Fibrosis

Abstract

Cardiovascular disease (CVD) stands as the foremost cause of patient mortality, and the lack of early diagnosis and defined treatment targets significantly contributes to the suboptimal prevention and management of CVD. Myocardial fibrosis (MF) is not only a complex pathogenic process with no effective treatment currently available but also exerts detrimental effects on the progression of various cardiovascular diseases, thereby escalating their mortality rates. Exosomes are nanoscale biocommunication vehicles that facilitate intercellular communication by transporting bioactive substances, such as nucleic acids and proteins, from specific cell types. Numerous studies have firmly established that microRNAs (miRNAs), as non-coding RNAs, wield post-transcriptional regulatory mechanisms and exhibit close associations with various CVDs, including coronary heart disease (CHD), atrial fibrillation (AF), and heart failure (HF). MiRNAs hold significant promise in the diagnosis and treatment of cardiovascular diseases. In this review, we provide a concise introduction to the biological attributes of exosomes and exosomal miRNAs. We also explore the roles and mechanisms of distinct cell-derived exosomal miRNAs in the context of myocardial fibrosis. These findings underscore the pivotal role of exosomes in the diagnosis and treatment of cardiac fibrosis and emphasize their potential as biotherapies and drug delivery vectors for cardiac fibrosis treatment.

Keywords: cardiac fibrosis; cardiovascular diseases; exosomes; extracellular vesicles; miRNA.

Figure 1

The relationship between myocardial fibrosis and various diseases. Excessive proliferation of cardiac fibroblasts or differentiation into myofibroblasts will cause increased extracellular matrix deposition. When the extracellular matrix environment is not balanced, myocardial fibrosis occurs, leading to various diseases.

Figure 2

The composition of exosome. Exosomes ranging in size from 30 to 200 nm contain a large number of proteins, including membrane transport proteins such as RAB GTPases, annexins, flotillins, ALIX from multivesicular bodies (MVBs), and TSG101. In addition, exosomes host tetraspanin transmembrane proteins, such as CD9, CD63, and CD81, and heat shock proteins, including HSP60 and HSP90. Furthermore, exosomes encapsulate a variety of nucleic acids, such as miRNA, mRNA, lncRNA, tRNA, snRNA, snoRNA, and circRNA, and lipids.

Figure 3

The secretion of exosomal miRNA. Firstly, miRNAs are selectively encased in MVBs, and then MVBs fuse with the donor cell membrane to release exosomes into the extracellular environment. Secondly, the target cells internalize the exosomes attached to the cell membrane through endocytosis, and finally release their contents into the cell. The released miRNA specifically binds to the 3′UTR of the target mRNA and inhibits the expression of the target gene.