Advances in MicroRNA Therapy for Heart Failure: Clinical Trials, Preclinical Studies, and Controversies

Heart failure (HF) is a rapidly growing public health issue with more than 37.7 million patients worldwide and an annual healthcare cost of $108 billion. However, HF-related drugs have not changed significantly for decades, and it is essential to find biological drugs to provide better treatment for HF patients. MicroRNAs (miRNAs) are non-coding RNAs (ncRNAs) with a length of approximately 21 nucleotides and play an important role in the onset and progression of cardiovascular diseases. Increasing studies have shown that miRNAs are widely involved in the pathophysiology of HF, and the regulation of miRNAs has promising therapeutic effects. Among them, there is great interest in miRNA-132, since the encouraging success of anti-miRNA-132 therapy in a phase 1b clinical trial in 2020. However, it is worth noting that the multi-target effect of miRNA may produce side effects such as thrombocytopenia, revascularization dysfunction, severe immune response, and even death. Advances in drug delivery modalities, delivery vehicles, chemical modifications, and plant-derived miRNAs are expected to address safety concerns and further improve miRNA therapy. Here, we reviewed the preclinical studies and clinical trials of HF-related miRNAs (especially miRNA-132) in the past 5 years and summarized the controversies of miRNA therapy.