The emerging role of microRNAs in hypoxia-induced pulmonary hypertension.

PURPOSE: The aim of this review is to discuss hypoxia-induced pulmonary hypertension (PH) and the role of microRNAs (miRNAs).

BACKGROUND: Acute global hypoxia causes pulmonary vasoconstriction and increased pulmonary arterial blood pressure. Chronic exposure to sustained or intermittent hypoxia as in high altitude residents, chronic obstructive lung disease and sleep-disordered breathing can lead to pulmonary hypertension (PH) and right ventricular dysfunction. The development of PH is a poor prognostic sign in these patients that affects both quality of life and mortality. The mechanism of PH due to hypoxia has not been fully established. However, its pathophenotype is similar to idiopathic pulmonary arterial hypertension in the form of vascular cell proliferation and aberrant vascular remodeling. MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression, therefore potentially regulating a host of cellular signaling pathways. Several miRNAs have been identified to be involved in hypoxia models of PH in animals, in patients with PH, congestive heart failure and myocardial infarction.

RESULTS: MiRNAs have been mechanistically linked to the control of a wide range of cellular responses-hypoxia, TGF-β signaling and inflammatory pathways-known to influence normal developmental physiology as well as regulating pulmonary arterial smooth muscle cell and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of hypoxia and pulmonary arterial hypertension (PAH). The blood levels of these miRNAs correlate with disease severity and prognosis.

CONCLUSIONS: Research on the role of these potential biomarkers will provide insight into the pathogenesis of PH and right heart failure and opportunities in therapeutics.