Differential display identification of 40 genes with altered expression inactivated human smooth muscle cells - Local expression in atherosclerotic lesions of smags, smooth muscle activation-specific genes

Detailed knowledge on the molecular and cellular mechanisms that control (r e)-differentiation of vascular smooth muscle cells (SMCs) is critical to un derstanding the pathological processes underlying atherogenesis. We identif ied by differential display/reverse transcriptase-polymerase chain reaction 40 genes with altered expression in cultured SMCs upon stimulation with th e conditioned medium of activated macrophages, This set of genes comprises 10 known genes and 30 novel genes, which we call "smags" (for smooth muscle activation-specific genes). To determine the in vivo significance of these (novel) genes in atherogenesis, we performed in situ hybridization experim ents on vascular tissue, Specifically, FLICE (Fas-associated death domain-l ike interleukin-1 beta-converting enzyme)-like inhibitory protein (FLIP) is expressed in neointimal SMCs as well as in lesion macrophages and endothel ial cells, whereas the expression of the novel genes smag-63, smag-64, and smag-84 is restricted to neointimal SMCs. Characterization of full-length s mag-64 cDNA revealed that it encodes a novel protein of 66 amino acids. sma g-82 cDNA comprises the complete, unknown, 3'-untranslated region of fibrob last growth factor-5, Collectively, our results illustrate the complex chan ges of SMC gene expression that occur in response to stimulation with cytok ines and growth factors secreted by activated macrophages, Moreover, we ide ntified interesting candidate genes that may play a role in the differentia tion of SMCs during atherogenesis.