tretinoin and Vascular-Calcification

Retinoic acid (RA) is a ligand for nuclear receptors that modulate gene transcription and cell differentiation. Whether RA controls ectopic calcification in humans is unknown. We tested the hypothesis that RA regulates osteogenic differentiation of human arterial smooth muscle cells and aortic valvular interstitial cells that participate in atherosclerosis and heart valve disease, respectively. Approach and Results: Human cardiovascular tissue contains immunoreactive RAR (RA receptor)-a retinoid-activated nuclear receptor directing multiple transcriptional programs. RA stimulation suppressed primary human cardiovascular cell calcification while treatment with the RAR inhibitor AGN 193109 or. These results establish retinoid regulation of human cardiovascular calcification, provide new insight into mechanisms involved in these responses, and suggest selective retinoid modulators, like acyclic retinoids may allow for treating cardiovascular calcification without the adverse effects associated with cyclic retinoids.

Topics: Alkaline Phosphatase; Aortic Valve; Apolipoprotein C-III; Calcium-Binding Proteins; Carotid Arteries; Carrier Proteins; Cells, Cultured; Cholesterol 7-alpha-Hydroxylase; Coronary Vessels; Extracellular Matrix Proteins; Heart Valve Diseases; Humans; Isotretinoin; Matrix Gla Protein; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Osteogenesis; Receptors, Retinoic Acid; Retinoids; Signal Transduction; Tretinoin; Vascular Calcification