When MicroRNAs meet hypoxic pulmonary hypertension

Hypoxic pulmonary hypertension (HPH) is a severe cardiovascular disease characterized by abnormal structural and functional remodeling of the pulmonary vasculature induced by chronic hypoxia, leading to a persistent increase in pulmonary vascular resistance and progressive right heart failure. It frequently complicates chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease. Its high prevalence, disability rate, and mortality pose significant global public health challenges in the cardiovascular field. Current HPH treatments are largely palliative and lack curative interventions capable of reversing vascular remodeling, primarily because of an insufficient understanding of the underlying pathological mechanisms and a scarcity of highly specific diagnostic markers and precisely targeted therapeutic agents. MicroRNAs (miRNAs), a class of endogenous noncoding RNAs approximately 20-24 nucleotides in length, regulate target gene expression at the posttranscriptional level. They play central regulatory roles in key pathological processes of HPH, including abnormal pulmonary vasoconstriction, an imbalance in smooth muscle cell proliferation and apoptosis, endothelial-Mesenchymal transition (EndMT), the activation of inflammatory responses, and metabolic reprogramming. This review systematically summarizes recent research advances concerning miRNAs in HPH, focusing on their regulatory networks in the pathogenesis of HPH-including pulmonary vasoconstriction, vascular remodeling, inflammation, and metabolic reprogramming-and their clinical value as diagnostic and prognostic biomarkers and therapeutic strategies targeting miRNAs along with their translational prospects. It also provides an in-depth analysis of current research challenges and future directions, aiming to offer a theoretical foundation for mechanistic studies and clinical translation in HPH.