Epitranscriptome in Ischemic Cardiovascular Disease: Potential Target for Therapies

Abstract

The global risk of cardiovascular disease, including ischemic disease such as stroke, remains high, and cardiovascular disease is the cause of one-third of all deaths worldwide. The main subjacent cause, atherosclerosis, is not fully understood. To improve early diagnosis and therapeutic strategies, it is crucial to unveil the key molecular mechanisms that lead to atherosclerosis development. The field of epitranscriptomics is blossoming and quickly advancing in fields like cancer research, nevertheless, poorly understood in the context of cardiovascular disease. Epitranscriptomic modifications are shown to regulate the metabolism and function of RNA molecules, which are important for cell functions such as cell proliferation, a key aspect in atherogenesis. As such, epitranscriptomic regulatory mechanisms can serve as novel checkpoints in gene expression during disease development. In this review, we describe examples of the latest research investigating epitranscriptomic modifications, in particular A-to-I editing and the covalent modification N 6 -methyladenosine and their regulatory proteins, in the context of cardiovascular disease. We additionally discuss the potential of these mechanisms as therapeutic targets and novel treatment options.

Unveiling blood pressure‐associated genes in aortic cells through integrative analysis of GWAS and RNA modification‐associated variants

“…m 6 A is a type of dynamic and reversible RNA modification that plays critical roles in gene expression regulation 29 and mRNA stability 30 and homeostasis 31 . RNA modification is involved in disease development and can be used in the clinic 32 . However, the role of RNA modification in BP regulation is unknown.…”

“… 31 RNA modification is involved in disease development and can be used in the clinic. 32 However, the role of RNA modification in BP regulation is unknown. In the present study, we showed that searching for RNAm‐SNPs in genomic loci was essential for a better understanding of GWAS signals.…”

RNA methylation pattern and immune microenvironment characteristics mediated by m6A regulator in ischemic stroke

“…When stimulated by lipopolysaccharides, YTHDF2-deficient macrophages can activate the MAPK and NF-κB signaling pathways and enhance the expression levels of signaling molecules, particularly TNF-α, IL-1β, IL-6, and IL-12 ( Yu et al, 2019 ). METTL3-deficient macrophages suppress oxLDL-induced m6A levels and inflammatory responses ( Quiles-Jiménez et al, 2022 ). m6A regulators also play a critical role in macrophage polarization.…”