Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jan 26:23:1136-1160.
doi: 10.1016/j.omtn.2021.01.024. eCollection 2021 Mar 5.

Targeting the epigenome in in-stent restenosis: from mechanisms to therapy

Xi Yang  1 , Yanyan Yang  2 , Junjie Guo  1 , Yuanyuan Meng  3 , Min Li  4 , Panyu Yang  3 , Xin Liu  1 , Lynn Htet Htet Aung  4 , Tao Yu  3   4 , Yonghong Li  1
Affiliations
Review

Targeting the epigenome in in-stent restenosis: from mechanisms to therapy

Xi Yang et al. Mol Ther Nucleic Acids. .

Abstract

Coronary artery disease (CAD) is one of the most common causes of death worldwide. The introduction of percutaneous revascularization has revolutionized the therapy of patients with CAD. Despite the advent of drug-eluting stents, restenosis remains the main challenge in treating patients with CAD. In-stent restenosis (ISR) indicates the reduction in lumen diameter after percutaneous coronary intervention, in which the vessel's lumen re-narrowing is attributed to the aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) and dysregulation of endothelial cells (ECs). Increasing evidence has demonstrated that epigenetics is involved in the occurrence and progression of ISR. In this review, we provide the latest and comprehensive analysis of three separate but related epigenetic mechanisms regulating ISR, namely, DNA methylation, histone modification, and non-coding RNAs. Initially, we discuss the mechanism of restenosis. Furthermore, we discuss the biological mechanism underlying the diverse epigenetic modifications modulating gene expression and functions of VSMCs, as well as ECs in ISR. Finally, we discuss potential therapeutic targets of the small molecule inhibitors of cardiovascular epigenetic factors. A more detailed understanding of epigenetic regulation is essential for elucidating this complex biological process, which will assist in developing and improving ISR therapy.

Keywords: DNA methylation; epigenetics; histone modification; in-stent restenosis; non-coding RNAs; target therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Overview of risk factors, pathogenesis, epigenetic regulation, and currently available targeted inhibitors associated with restenosis Targeted inhibitors are shown may address pathophysiological pathways associated with the formation and development of restenosis following stenting in coronary artery disease.
Figure 2
Figure 2
Illustrations of various epigenetic posttranslational modifications The nucleosome is comprised of approximately 147 bp of DNA comprising an octamer of two copies of each of the four core histone proteins H2A, H2B, H3, and H4. The histone tail is specifically modified by writing an enzyme that adds or erases the PTM shown.
Figure 3
Figure 3
Image representing the hypothetical structure of a stent capable of eluting a targeted inhibitor The scaffold surface is coated with polylactic acid-glycolic acid copolymer (PLGA). At the bottom of the figure are listed targeted regulatory inhibitors that have the potential to be regulated for therapeutic use.
See this image and copyright information in PMC

References

    1. Benjamin E.J., Muntner P., Alonso A., Bittencourt M.S., Callaway C.W., Carson A.P., Chamberlain A.M., Chang A.R., Cheng S., Das S.R., American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics–2019 update: a report from the American Heart Association. Circulation. 2019;139:e56–e528. - PubMed
    1. Roth G.A., Abate D., Abate K.H., Abay S.M., Abbafati C., Abbasi N., Abbastabar H., Allah F.A., Abdela J., Abdelalim A., GBD 2017 Causes of Death Collaborators Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1736–1788. - PMC - PubMed
    1. Canfield J., Totary-Jain H. 40 years of percutaneous coronary intervention: history and future directions. J. Pers. Med. 2018;8:33. - PMC - PubMed
    1. Borovac J.A., D’Amario D., Vergallo R., Porto I., Bisignani A., Galli M., Annibali G., Montone R.A., Leone A.M., Niccoli G., Crea F. Neoatherosclerosis after drug-eluting stent implantation: a novel clinical and therapeutic challenge. Eur. Heart J. Cardiovasc. Pharmacother. 2019;5:105–116. - PubMed
    1. Park S.J., Kang S.J., Virmani R., Nakano M., Ueda Y. In-stent neoatherosclerosis: a final common pathway of late stent failure. J. Am. Coll. Cardiol. 2012;59:2051–2057. - PubMed

LinkOut - more resources