Recent advances in mechanistic studies of heart failure with preserved ejection fraction and its comorbidities—Role of microRNAs

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome with a complex aetiology commonly associated with comorbidities such as diabetes mellitus, obesity, hypertension and renal disease. Various diseases induce systemic, chronic and low-grade inflammation; microvascular dysfunction; metabolic stress; tissue ischemia; and fibrosis, leading to HFpEF. An effective treatment for HFpEF is lacking, largely owing to its pathophysiological heterogeneity. Recent studies have revealed that microRNAs (miRNAs) play crucial roles in regulating the pathogenesis of HFpEF and its comorbidities. METHODS: This narrative review included original articles and reviews published over the past 20 years found through 'PubMed' and 'Web of Science'. The search terms included "HFpEF," "MicroRNAs," "comorbidities," "Microvascular Dysfunction (MVD)," "inflammation," "pathophysiology," "endothelial dysfunction," "energy metabolism abnormalities" "cardiac fibrosis" and "treatment." RESULTS: Inflammation, MVD, abnormal energy metabolism, myocardial hypertrophy and myocardial fibrosis are important pathophysiological mechanisms underlying HFpEF. As gene expression regulators, miRNAs may contribute to the pathophysiology of HFpEF and are expected to serve in the stratification of patients with HFpEF and as prognostic indicators for monitoring treatment responses. CONCLUSIONS: A customized strategy based on miRNAs has emerged as an effective treatment for HFpEF. In this review, we discuss recent research surrounding miRNAs and HFpEF and propose potential miRNA targets for the pathophysiology of HFpEF and its comorbidities. Although current research concerning miRNAs and their therapeutic potential is in its early stages, miRNA-based diagnostics and therapeutics hold great promise in the future.