Cultured porcine coronary artery smooth muscle cells - A new model with advanced differentiation

Arterial intimal thickening after endothelial injury induced in rodents has proven to be a relatively unreliable model of restenosis for testing clini cally useful compounds. The same has been found for cultured rat or rabbit vascular smooth muscle cells (SMCs). To test alternative possibilities, we have studied several differentiation features of porcine coronary artery SM Cs, cultured up to the 5th passage after enzymatic digestion of the media. The effects of heparin, transforming growth factor (TGF)-beta(1) or TGF-bet a(2), and all-trans-retinoic acid (tRA) on proliferation, migration, and di fferentiation of these cells also were examined. Porcine arterial SMCs in c ulture not only express high levels of alpha-smooth muscle (SM) actin but, contrary to rodent SMCs, also maintain an appreciable expression of SM myos in heavy chain isoforms 1 and 2, desmin, and smoothelin, a recently describ ed late differentiation marker of vascular SMCs. We demonstrate for the fir st time that smoothelin is colocalized with alpha-SM actin in these cells. Finally, we show that in the porcine model, heparin is more potent than TGF -beta(1) or TGF-beta(2) and tRA in terms of inhibition of proliferation and migration and of increasing the expression of differentiation markers. Thi s model should be a useful complement to in vivo studies of SMC differentia tion and of pathological situations such as restenosis and atheromatosis.