Harnessing mRNA technology for ischemic heart disease: a review of regenerative and protective therapies.

Abstract

As ischemic heart disease (IHD) remains the leading cause of mortality worldwide, there is an urgent need for innovative therapies that go beyond symptom management. The irreversible damage to cardiac tissue following myocardial infarction (MI) and the limited regenerative and proliferative capacity of adult cardiomyocytes (CMs) present significant challenges to the development of treatments capable of restoring cardiac function. This review focuses on emerging modified and non-modified messenger ribonucleic acid (mRNA)-based therapies, which offer targeted and transient protein expression. The studies reviewed here address three major therapeutic strategies: cardiac regeneration, aimed at inducing CM proliferation to restore lost cardiac muscle; cardiac protection, centered on anti-apoptotic and anti-inflammatory methods to mitigate further tissue damage; and cardiovascular regeneration, focused on promoting angiogenesis and restoring vascular integrity after injury. By examining mRNA and modified mRNA (modRNA) therapies across these three approaches, this review showcases mRNA's promising role in advancing muscular and vascular regenerative and protective therapeutics for IHD.