The role of exosomal lncRNAs in cardiovascular disease: Emerging insights based on molecular mechanisms and therapeutic target level

Abstract

Cardiovascular diseases (CVD) are widely recognized as a leading cause of death worldwide; however, early diagnosis and disease progression monitoring play a crucial role in their clinical management. The common diagnostic and prognostic biomarkers have represented a revolutionary tool for studying CVD; however, their applications are limited to invasive irreversible heart diseases, such as drug-induced myocardial injury. In light of this information, a growing number of studies are currently investigating the diagnostic and prognostic potential of novel CVD biomarkers. Examples of this are long non-coding RNA (lncRNA) and other RNAs that are specifically expressed at the early stages of heart disease. These RNAs have been reported to be involved in the development of CVD via activating or inhibiting inflammatory mediators and angiogenesis-related factors, as well as endothelial cell proliferation, migration and phenotypic transformation. This review collectively summarizes the recent studies' results concerning exosomal lncRNA biogenesis, characterization, and function, as well as its role as a novel biomarker in a variety of CVD.

Keywords: Biomarkers; Cardiovascular diseases; Drugs; Exosomes; LncRNA.

Fig. 1

Exosome hallmarks and biochemical roles. Exosome characteristics. Exosomes contain proteins, nucleic acids, lipids and other biological information molecules, which mediate the communication between cells through their specific pathways, and then affect the disease state.

Fig. 2

Multiple mechanisms involved in the regulation of MVB formation [30]. ILV promotes the formation of polyvesicles (MVB) under the action of ESCRT complex. 1: ESCRT-0, -I, -II, -III and VPS4 synergistically regulate the formation of ILV. 2: Alix and HD-PTP recruit ESCRT-III or VPS4 to limit the membrane formation of MVB. Under S1P signal transduction, CDC42 and Rac1 are continuously activated to facilitate cargo sorting to ILV. In addition, some important lipid raft components such as flotillin and caveolins also drive ILV formation. In summary, ESCRTs interact with related proteins or specific lipid molecules to promote exosome sorting in dependent and independent manners.