MicroRNA-99a

Abstract

R eactive oxygen species (ROS) are continuously formed in myocardium as a byproduct of mitochondrial oxidative phosphorylation, and are also produced by several enzymes such as NADPH oxidases, xanthine oxidase, and uncoupled endothelial NO synthase.1,2) In normal cardiovascular physiology, ROS act as essential signaling molecules that modulate the activity of many bioactive molecules including protein kinases, phosphatases, transcription factors, and cytoskeletal proteins.3) However, excessive and aberrant production of ROS during pathological oxidative stress can cause cellular dysfunction and death by inducing irreversible damage of organelles and macromolecules such as lipids, proteins, and DNA.1,2) An increasing body of evidence has suggested that oxidative stress is crucially involved in the pathogenesis and progression of a wide range of cardiovascular diseases.1,2) For example, it was reported that the myocardial ROS levels were elevated in animal models of ischemia-reperfusion injury 2,4) and heart failure, 5) and that a number of antioxidant strategies using ROS scavengers provided cardioprotection in these animal models.2) However, clinical interventions by treatment with antioxidants have proven to be ineffective or even harmful for patients with cardiovascular diseases.2,6) Rather than simple antioxidant strategies, a strategy to reduce pathological oxidative stress without altering physiological ROS signaling will put forward the translation of ROS modulation into the clinic. 7)