The Emerging Role of microRNAs as Targets of Phytochemical Intervention in Myocardial Infarction: A Systematic Review of In Vitro and In Vivo Studies

This systematic review evaluates the current literature on the protective mechanisms of dietary phytochemicals in cellular and animal models of myocardial infarction, with a specific focus on miRNA modulation. A literature search was conducted across three databases (PubMed, Scopus, and Embase) in accordance with PRISMA guidelines. Studies published in English between 2014 and 2024 were included based on predefined keywords. Of 432 identified records, 28 articles met the inclusion criteria and were included in the review. The results showed that phytochemicals upregulated 20 different miRNAs (e.g., miR-21, miR-126, and miR-24-3p) and downregulated 10 others (e.g., miR-34a and miR-155-5p). These changes in miRNA expression were associated with reduced ischemia-induced apoptosis (e.g., decreased cleaved caspase-3 or BAX levels), inflammation (e.g., decreased levels of pro-inflammatory interleukins), and oxidative stress (e.g., increased antioxidant enzyme activity). In addition, phytochemicals modulated autophagy (e.g., decreased Beclin-1 and LC3-II levels or increased p62 levels) and activated pro-survival pathways such as PI3K/Akt signaling. Overall, our analysis suggests that targeting miRNA pathways with phytochemicals may mitigate ischemic injury, as shown by increased cell viability and reduced myocardial infarct size. This approach may therefore support the development of new nutritional and therapeutic strategies for myocardial infarction. However, because all included studies were conducted in preclinical models, clinical trials in humans are required to validate these findings.