Extracellular vesicles in atherosclerosis and vascular calcification: the versatile non-coding RNAs from endothelial cells and vascular smooth muscle cells

Abstract

Atherosclerosis (AS) is characterized by the accumulation of lipids, fibrous elements, and calcification in the innermost layers of arteries. Vascular calcification (VC), the deposition of calcium and phosphate within the arterial wall, is an important characteristic of AS natural history. However, medial arterial calcification (MAC) differs from intimal calcification and cannot simply be explained as the consequence of AS. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are directly involved in AS and VC processes. Understanding the communication between ECs and VSMCs is critical in revealing mechanisms underlying AS and VC. Extracellular vesicles (EVs) are found as intercellular messengers in kinds of physiological processes and pathological progression. Non-coding RNAs (ncRNAs) encapsulated in EVs are involved in AS and VC, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). The effects of ncRNAs have not been comprehensively understood, especially encapsulated in EVs. Some ncRNAs have demonstrated significant roles in AS and VC, but it remains unclear the functions of the majority ncRNAs detected in EVs. In this review, we summarize ncRNAs encapsulated in EC-EVs and VSMC-EVs, and the signaling pathways that are involved in AS and VC.

Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis

“…In the intima, SMCs may differentiate into macrophage-like foam cells or osteocytes, leading to intimal calcification [44]. Vascular calcification could be positively (miR-670-3p, miR-3182) or negatively (miR-29b, miR-126-5p) regulated by microRNAs encapsulated into cell-derived extracellular vesicles [45][46][47]. Microcalcifications are the most harmful and are associated with plaque inflammation, which persists throughout advanced lesions with the release of proinflammatory cytokines (IL-1β, IL-6, TNFα) and the risk of plaque rupture [48].…”

Pathogenesis and Mechanism of Uremic Vascular Calcification

“…This result indicates that HP-HUVEC-Exo has calcium-promoting effects [ 87 ]. In addition to target proteins, miRNAs encapsulated in EC-EVs have been demonstrated to modulate blood vessels in CKD-MBD, with miR-143-3p and miR-145-5p inhibiting VC and miR-221-3p and miR-222-3p enhancing VC [ 88 ].…”

Extracellular Vesicles in Atherosclerosis: State of the Art

“…coding RNAs (lncRNAs), and circular RNAs (circRNAs), which are encapsulated in EVs, are involved in AS and VC [76,77]. ncRNAs shuttled via EVs may control post-hypoxia tissue survival and remodeling by regulating cell injury and inflammatory responses in MI and stroke [78,79].…”

“…They can also reduce hypertension by regulating the VSMC phenotype via the ACE2/NF-κB/Ang II pathway [ 75 ]. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), which are encapsulated in EVs, are involved in AS and VC [ 76 , 77 ]. ncRNAs shuttled via EVs may control post-hypoxia tissue survival and remodeling by regulating cell injury and inflammatory responses in MI and stroke [ 78 , 79 ].…”