The Role of Exosomal Non-Coding RNAs in Coronary Artery Disease

Abstract

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. Atherosclerosis (AS) is a major cause of CVD. Oxidative stress, endothelial dysfunction, and inflammation are key factors involved in the development and progression of AS. Exosomes are nano-sized vesicles secreted into the extracellular space by most types of cells, and are ideal substances for the transmission and integration of signals between cells. Cells can selectively encapsulate biologically active substances, such as lipids, proteins and RNA in exosomes and act through paracrine mechanisms. Non-coding RNAs (ncRNAs) are important for communication between cells. They can reach the recipient cells through exosomes, causing phenotypic changes and playing a molecular regulatory role in cell function. Elucidating their molecular mechanisms can help identify therapeutic targets or strategies for CVD. Coronary artery disease (CAD) is the most important disease in CVD. Here, we review the role and the regulatory mechanism of exosomal ncRNAs in the pathophysiology of CAD, as well as the potential contribution of exosomal ncRNA to diagnosis and treatment of CAD.

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

“…The communication between exosomal miRNAs and ECs plays a vital role in the pathogenesis of AS. 436 Exosomal miR-92a, upregulated by the combination of low shear stress and oxidized LDL in atherosclerotic mice model, promoted endothelial inflammation and atherosclerotic plaque formation. 437 Besides, Xing et al reported that exosomal miR-342-5p released by adipose-derived MSCs exerted an anti-atherosclerotic effect by promoting H 2 O 2 -induced ECs apoptosis and protecting against ECs injury.…”

NcRNAs in Vascular and Valvular Intercellular Communication

“…To analyze and quantify ncRNAs in exosomes and microvesicles, they must be isolated from platelet-depleted plasma (Liu et al, 2020). Isolation techniques differ between ncRNAs transported in EVs and those transported in ncRNAprotein complexes (Liu et al, 2020).…”

“…To analyze and quantify ncRNAs in exosomes and microvesicles, they must be isolated from platelet-depleted plasma (Liu et al, 2020). Isolation techniques differ between ncRNAs transported in EVs and those transported in ncRNAprotein complexes (Liu et al, 2020). A commonly used technique is differential centrifugation, although a variety of isolation methods are applied (Witwer et al, 2013).…”

“…Yield and purity differ immensely between different approaches as well as between research groups (E et al, 2018), and the low concentration of protein-ncRNA complexes can make quantification difficult (Gallo et al, 2012). While differential ultracentrifugation is an established method, it is time consuming and demands large sample sizes, while only producing a low recovery rate, thus making it impractical in large scale clinical settings (Liu et al, 2020). Other techniques, better suited for small sample sizes, such as spectrofluorimetry and capillary electrophoresis are more expensive and even more time consuming, and thus also not feasible in a high throughput diagnostic setting (E et al, 2018;Gallo et al, 2012).…”

“…However, increased mechanical sheer may break vesicles and influence results. With exosomes derived from the endocytic pathway and microvesicles formed from the plasma membrane, they express different CD-markers, making immunocapture-assays another potential route for isolation (Liu et al, 2020).…”