The therapeutic potential of miRNAs regulated in settings of physiological cardiac hypertrophy.
Cardiac hypertrophy is broadly defined as an increase in heart mass. Heart enlargement in a setting of cardiac disease is referred to as pathological hypertrophy and often progresses to heart failure. Physiological hypertrophy refers to heart growth in response to postnatal development, exercise training and pregnancy, and is an adaptive response associated with the activation of cardioprotective signaling cascades. miRNAs have emerged as novel therapeutic targets for numerous pathologies, and miRNA-based therapies have already entered clinical trials. The identification of miRNAs differentially regulated during physiological growth may open up new therapeutic approaches for heart failure. In this review, we present information on miRNAs regulated in models of physiological hypertrophy, describe preclinical cardiac disease studies that have successfully targeted miRNAs regulated in settings of physiological growth (miR-34, miR-15, miR-199b, miR-208a and miR-378), and discuss challenges to overcome for the safe entry of miRNA-based therapies into the clinic for heart failure patients.
Baker IDI Heart & Diabetes Institute, PO Box 6429, St Kilda Road Central, Melbourne 8008, Australia.
Jenny Y Y
JY
Ooi
Bianca C
BC
Bernardo
Julie R
JR
McMullen
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D005260:Female; D006321:Heart / Q000254:growth & development / Q000502:physiology; D006526:Hepatitis C / Q000628:therapy; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D010805:Physical Conditioning, Animal; D011247:Pregnancy; D015398:Signal Transduction
D035683:MicroRNAs