The Long Non-coding Road to Atherosclerosis

Abstract

Purpose of Review To summarize recent insights into long non-coding RNAs (lncRNAs) involved in atherosclerosis. Because atherosclerosis is the main underlying pathology of cardiovascular diseases (CVD), the world's deadliest disease, finding novel therapeutic strategies is of high interest. Recent Findings LncRNAs can bind to proteins, DNA, and RNA regulating disease initiation and plaque growth as well as plaque stability in different cell types such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages. A number of lncRNAs have been implicated in cholesterol homeostasis and foam cell formation such as LASER, LeXis, and CHROME. Among others, MANTIS, lncRNA-CCL2, and MALAT1 were shown to be involved in vascular inflammation. Further regulations include, but are not limited to, DNA damage response in ECs, phenotypic switch of VSMCs, and various cell death mechanisms. Interestingly, some lncRNAs are closely correlated with response to statin treatment, such as NEXN-AS1 or LASER. Additionally, some lncRNAs may serve as CVD biomarkers. Summary LncRNAs are a potential novel therapeutic target to treat CVD, but research of lncRNA in atherosclerosis is still in its infancy. With increasing knowledge of the complex and diverse regulations of lncRNAs in the heterogeneous environment of atherosclerotic plaques, lncRNAs hold promise for their clinical translation in the near future.

Regulation of Long Non-Coding RNAs by Statins in Atherosclerosis

“…Several lncRNAs have been implicated in atherosclerosis ( Table 1 ). Their mechanism of action is somewhat complicated since lncRNA may act on multiple levels and exert atheroprotective or atherogenic effects ( Figure 1 ) [ 9 ].…”

“…Long noncoding RNAs (lncRNAs) are transcripts of long RNAs of more than 200 nucleotides that are not translated into proteins [ 8 ]. Accumulating evidence shows that lncRNAs essentially contribute to the regulation of gene expression and play an important role in vascular biology, endothelial cell (EC) function, and the development of vascular disease [ 9 , 10 , 11 ]. The current literature suggests that lncRNAs might be up- or downregulated among patients with atherosclerosis, including coronary artery disease (CAD), peripheral artery disease, or carotid disease [ 9 , 10 , 11 ].…”

“…Accumulating evidence shows that lncRNAs essentially contribute to the regulation of gene expression and play an important role in vascular biology, endothelial cell (EC) function, and the development of vascular disease [ 9 , 10 , 11 ]. The current literature suggests that lncRNAs might be up- or downregulated among patients with atherosclerosis, including coronary artery disease (CAD), peripheral artery disease, or carotid disease [ 9 , 10 , 11 ]. To date, numerous lncRNAs have been implicated in certain atherogenic processes, including endothelial dysfunction, lipid deposition, and inflammation [ 9 , 10 , 11 , 12 ].…”

“…The current literature suggests that lncRNAs might be up- or downregulated among patients with atherosclerosis, including coronary artery disease (CAD), peripheral artery disease, or carotid disease [ 9 , 10 , 11 ]. To date, numerous lncRNAs have been implicated in certain atherogenic processes, including endothelial dysfunction, lipid deposition, and inflammation [ 9 , 10 , 11 , 12 ]. In addition, lncRNAs have been demonstrated to be expressed in different cell types known to be implicated in the atherogenic process (e.g., ECs, vascular smooth muscle cells [VSMCs], and macrophages) [ 9 , 12 ].…”

“…To date, numerous lncRNAs have been implicated in certain atherogenic processes, including endothelial dysfunction, lipid deposition, and inflammation [ 9 , 10 , 11 , 12 ]. In addition, lncRNAs have been demonstrated to be expressed in different cell types known to be implicated in the atherogenic process (e.g., ECs, vascular smooth muscle cells [VSMCs], and macrophages) [ 9 , 12 ]. Although significant progress has been made in characterizing lncRNAs that are implicated in atherosclerosis, it is estimated that fewer than 5% have been identified to date.…”