Noncoding RNA as potential therapeutics to rescue mitochondrial dysfunction in cardiovascular diseases

Noncoding RNAs (ncRNAs) are critical regulators of mitochondrial function in cardiovascular diseases. Several studies have explored the manipulation of ncRNAs in mitochondrial dysfunction in different cardiovascular disease contexts, however, there is a dearth of information on the exploration of these noncoding RNAs as actual therapeutics to ameliorate cardiovascular diseases. This systematic review examines the roles of various ncRNAs in modulating mitochondrial dysfunction across major cardiovascular diseases and how they can be targeted to the mitochondria. A comprehensive literature search was conducted using Web of Science and Scopus databases, following the PRISMA guidelines. Original research articles in the English language, focusing on ncRNAs and mitochondrial dysfunction in specific cardiovascular diseases, were eligible for inclusion. A total of 76 studies were included in the systematic review with up to 100 ncRNAs identified as therapeutic biomarkers. The identified ncRNAs participate in regulating mitochondrial processes including oxidative phosphorylation (OXPHOS), fission/fusion dynamics, apoptosis, and calcium handling in cardiovascular diseases. Mitochondrial targeting moieties including mitochondrial targeting cell-penetrating peptides, mitochondrial targeting liposomes, and aptamers can be conjugated to ncRNAs and delivered to the heart via various injection routes including the pericardium or the myocardium. However, significant challenges remain in developing effective delivery methods to modulate these ncRNAs in vivo.