Non-coding RNAs in cardiovascular cell biology and atherosclerosis

Abstract

Atherosclerosis underlies the predominant number of cardiovascular diseases and remains a leading cause of morbidity and mortality worldwide. The development, progression and formation of clinically relevant atherosclerotic plaques involves the interaction of distinct and over-lapping mechanisms which dictate the roles and actions of multiple resident and recruited cell types including endothelial cells, vascular smooth muscle cells, and monocyte/macrophages. The discovery of non-coding RNAs (ncRNAs) including microRNAs, long non-coding RNAs, and circular RNAs, and their identification as key mechanistic regulators of mRNA and protein expression has piqued interest in their potential contribution to atherosclerosis. Accruing evidence has revealed ncRNAs regulate pivotal cellular and molecular processes during all stages of atherosclerosis including cell invasion, growth, and survival; cellular uptake and efflux of lipids, expression and release of pro- and anti-inflammatory intermediaries, and proteolytic balance. The expression profile of ncRNAs within atherosclerotic lesions and the circulation have been determined with the aim of identifying individual or clusters of ncRNAs which may be viable therapeutic targets alongside deployment as biomarkers of atherosclerotic plaque progression. Consequently, numerous in vivo studies have been convened to determine the effects of moderating the function or expression of select ncRNAs in well-characterized animal models of atherosclerosis. Together, clinicopathological findings and studies in animal models have elucidated the multifaceted and frequently divergent effects ncRNAs impose both directly and indirectly on the formation and progression of atherosclerosis. From these findings’ potential novel therapeutic targets and strategies have been discovered which may pave the way for further translational studies and possibly taken forward for clinical application.

Definition and review on a category of long non-coding RNA: Atherosclerosis-associated circulating lncRNA (ASCLncRNA)

“…LncRNAs widely distribute in various organs, tissues, and cells, and have important roles in different types of CVDs, such as CAD, AMI, and so on ( Huang, 2018 ). At present, the researches on lncRNAs in the occurrence and development of AS mainly focus on their effects on the lipid metabolism, aberrant proteolysis and cell activities such as impaired function of ECs, modulation of VSMCs’ phenotype, recruitment of inflammatory cells, the polarization of macrophages and formation of foam cell ( Fasolo et al, 2019 ; Li, Zhu & Ge, 2016 ; Zhou et al, 2016 ). In the last several years, the advance of high throughput sequencing technology brought about abundant novel transcripts with or without function annotation.…”

Identification of Susceptibility Loci for Cardiovascular Disease in Adults With Hypertension, Diabetes and Dyslipidemia 

“…The CBX gene family, a recent research interest in the eld of long noncoding RNAs, has been associated with CVD and atherosclerosis in multiple studies. [24,25] GAA gene expression has been found to be speci cally increased in CAD patients than in controls. [26] CARD14, which is mainly associated with psoriasis (ongoing clinical studies suggest increased risk of CVDs in psoriasis) and auto-in ammatory disorders, acts as a pro-in ammatory gene by affecting NF-kB activation in the IL-17 in ammation pathway.…”

“…RPTOR is a component of the mTOR pathway, which regulates cell growth in response to nutrient levels by associating with the mammalian target of rapamycin (mTOR). [34] New insights have been offered into RPTOR and CVD/atherosclerosis; such as evidence that miR-100 exerts anti-angiogenic properties through suppression of mTOR, [24] and that inhibition of cardiac GSK-3β during continued myocardial ischemia attenuates ischemia-induced mTORC1 inhibition and increases ischemic injury. [34] Rs139293840 (17q25.3/RPTOR, minor allele frequency (MAF) ~ 0.01) showed substantial risk for DM-CAD (OR 3.36 [2.06-5.48]); although the association was suggestive (P = 1.27 × 10 −6 ; however, genome-wide signi cance in DM-CCD, P = 1.99 × 10 -8 ), this could be due to insu cient statistical power after selecting populations for quality control.…”

Peer Review #1 of "Definition and review on a category of long non-coding RNA: Atherosclerosis-associated circulating lncRNA (ASCLncRNA) (v0.1)"

“…Given its good indicator role in cancer, we could expect the possibility of its clinical application in AS diagnosis and prognosis. (Fasolo et al 2019;Li et al 2016;Zhou et al 2016). In the last several years, the advance of high throughput sequencing technology brought about abundant novel transcripts with or without function annotation.…”