MYOCYTE ENHANCER-BINDING FACTOR-II EXPRESSION AND ACTIVITY IN VASCULAR SMOOTH-MUSCLE CELLS - ASSOCIATION WITH THE ACTIVATED PHENOTYPE

Proliferation and phenotypic modulation of smooth muscle cells (SMCs) are major components of the vessel's response to injury in experimenta l models of restenosis. Some of the growth factors involved in resteno sis have been identified, but to date little is known about the transc ription factors that ultimately regulate this process. We examined the expression of the four members of the myocyte enhancer binding factor -2 (MEF2) family of transcription factors in cultured rat aortic SMCs (RASMCs) and a rat model of restenosis because of their known importan ce in regulating the differentiated phenotype of skeletal and cardiac muscle. In skeletal and cardiac muscle, the MEF2s are believed to be i mportant for activating the expression of contractile protein and othe r muscle-specific genes. Therefore, we anticipated that the MEF2s woul d be expressed at high levels in medial SMCs that are producing contra ctile proteins and that they would be downregulated along with the con tractile protein genes in neointimal SMCs. On the contrary, we observe that MEF2A, MEF2B, and MEF2D mRNAs are upregulated in the neointima, with the highest levels in the layer of cells nearest to the lumen, wh ereas MEF2C mRNA levels do not appreciably increase. Moreover, few cel ls in the media are making MEF2 proteins detectable by immunohistochem istry, whereas large numbers of neointimal cells are positive for all four MEF2s. These data suggest that the MEF2s are involved in the acti vated smooth muscle phenotype and not in the maintenance of contractil e protein gene expression.