Identification of the ROR alpha Transcriptional Network Contributes to the Search for Therapeutic Targets in Atherosclerosis

The retinoic acid receptor-related orphan receptor alpha (ROR alpha) is involved in the regulation of several physiological processes, including development, metabolism, and circadian rhythm. ROR alpha-deficient mice display profound atherosclerosis, in which hypoalphalipoproteinemia is reportedly associated with decreased plasma levels of high-density lipoprotein, increased levels of inflammatory cytokines, and ischemia/reperfusion-induced damage. The recent characterization of endogenous ligands (including cholesterol, oxysterols, provitamin D3, and their derivatives), mediators, and initiation complexes associated with the transcriptional regulation of these orphan nuclear receptors has facilitated the development of synthetic ligands. These findings have also highlighted the potential of application of ROR alpha as a therapeutic target for several diseases, including diabetes, dyslipidemia, and atherosclerosis. In this review, the current literature related to the structure and function of ROR alpha, its genetic inter-individual differences, and its potential as a therapeutic target in atherosclerosis is discussed.