Heterogeneity of smooth muscle cells in advanced human atherosclerotic plaques: intimal smooth muscle cells expressing a fibroblast surface protein are highly activated by platelet-released products

Background In vascular disease, smooth muscle cells (SMC) undergo phenotypi c modulation and may acquire properties resembling those of fibroblasts in tissue wound healing. Aims We aimed to show the differential expression of a fibroblast surface p rotein (FSP) by SMC in atherosclerotic lesions. Results In early human coronary atherosclerotic lesions the expression of F SP in the intima was absent. In contrast, 29 of 29 middle/advanced lesions contained intimal SMC expressing high levels of FSP. Fibroblast surface pro tein positive SMC were negative for desmin but expressed variable levels of ce-SM actin, SM caldesmon, SM myosin heavy chain and vimentin. Explants fr om advanced atherosclerotic lesions yielded two main SMC subpopulations. SM C over-expressing FSP exhibited higher in vitro mitogenic response (premito tic DNA synthesis) to sera (2- to 8-fold) and platelet-released products (8 - to 26-fold), especially from thrombin-activated platelets, than FSP-negat ive SMC. Conclusions Our results suggest that the expression of FSP in SMC could ind icate an activated phenotype, and the presence of highly positive FSP cells in the atherosclerotic lesions might be indicative of an increased SMC res ponsiveness to processes that locally generate thrombin and activate platel ets.