Retinoids and Arterial Smooth Muscle Cells

Retinoic acid (RA), the active metabolite of vitamin A, isa crucial signaling molecule during vertebrate develop-ment and plays key roles in establishing cell lineages as well as in cell differentiation and proliferation.1 RA has been shown to influence the expression of many genes (see the Table) through interactions between RA receptors (RARs) and the RA response element (RARE) located in promoter regions.42,43 RARs, transducers of the RA signal at the gene expression level, are members of the nuclear receptor super-family. Essentially 2 subfamilies of nuclear receptor are known to function as RA-dependent transcription factors: the RARs and the retinoid X receptors (RXRs).44 These recep-tors, in the form of homodimers or heterodimers, recognize response elements located in the promoter regions of target genes. For each subfamily, 3 different genes (RAR-a,-b, and-g; RXR-a,-b, and-g) generate multiple isoforms with specific patterns of expression in both the embryo and adult,