HypoxamiRs: regulators of cardiac hypoxia and energy metabolism

• Hypoxia is increasingly considered as a characteristic of heart failure.
• Hypoxia is capable of driving global changes in cardiac mature miRNA expression profiles by altering miRNA biogenesis.
• Several hypoxamiRs are implicated in cardiac development and cardiac disease.
• New classes of RNA therapeutics based upon antisense RNA technology are opening new avenues to intervene at the level of hypoxia and cardiac remodeling.

Hypoxia and its intricate regulation are at the epicenter of cardiovascular research. Mediated by hypoxia-inducible factors as well as by several microRNAs, recently termed ‘hypoxamiRs’, hypoxia affects several cardiac pathophysiological processes. Hypoxia is the driving force behind the regulation of the characteristic metabolic switch from predominant fatty acid oxidation in the healthy heart to glucose utilization in the failing myocardium, but also instigates reactivation of the fetal gene program, induces the cardiac hypertrophy response, alters extracellular matrix composition, influences mitochondrial biogenesis, and impacts upon myocardial contractility. HypoxamiR regulation adds a new level of complexity to this multitude of hypoxia-mediated effects, rendering the understanding of the hypoxic response a fundamental piece in solving the cardiovascular disease puzzle.