MicroRNA Therapy for the Failing Heart
Heart failure (HF) may result from diverse pathological processes leading to progressive organ decompensation. Improper functionality of the calcium-handling machinery is a frequent component of the pathobiology underlying this debilitating process. Case in point, loss of intracellular calcium homeostasis because of decreased function of sarco/endoplasmic reticulum Ca2+-ATPase 2ª (SERCA2a) is characteristic of HF, and restoration of SERCA2a function through gene therapy results in improved cardiac performance.1 MicroRNAs (miRNAs) constitute a new family of fine-tuning molecules involved in tight regulation of physiological and pathological processes. In fact, the identity and the level of miRNAs expressed at the systemic and organ levels change with disease.
Wahlquist et al2 hypothesize that miRNAs capable of repressing contractility might be involved in HF and could, therefore, be used as therapeutic targets. Specifically, the authors focus their efforts on miRNAs involved in calcium dynamics regulation.
How Was the Hypothesis Tested?
To search for miRNAs capable of downregulating SERCA2a, a whole-genome collection of miRNAs was tested on Human Embryonic Kidney 293 cells cotransfected with an enhanced green fluorescent protein reporter fused to the 3′ untranslated region of the SERCA2A gene, enabling functional detection of miRNAs capable of decreasing SERCA2a through a fluorescence (enhanced green …