Novel Therapeutic Potential of Retinoid-Related Orphan Receptor alpha in Cardiovascular Diseases

The retinoid-related orphan receptor alpha (ROR alpha) is one subfamily of nuclear hormone receptors (NRs). This review summarizes the understanding and potential effects of ROR alpha in the cardiovascular system and then analyzes current advances, limitations and challenges, and further strategy for ROR alpha-related drugs in cardiovascular diseases. Besides regulating circadian rhythm, ROR alpha also influences a wide range of physiological and pathological processes in the cardiovascular system, including atherosclerosis, hypoxia or ischemia, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, hypertension, and myocardial hypertrophy. In terms of mechanism, ROR alpha was involved in the regulation of inflammation, apoptosis, autophagy, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial function. Besides natural ligands for ROR alpha, several synthetic ROR alpha agonists or antagonists have been developed. This review mainly summarizes protective roles and possible mechanisms of ROR alpha against cardiovascular diseases. However, there are also several limitations and challenges of current research on ROR alpha, especially the difficulties on the transformability from the bench to the bedside. By the aid of multidisciplinary research, breakthrough progress on ROR alpha-related drugs to combat cardiovascular disorder may appear.