PROLIFERATIVE RESPONSE OF HUMAN AND MINIPIG SMOOTH-MUSCLE CELLS AFTERCORONARY ANGIOPLASTY TO GROWTH-FACTORS AND PLATELETS

Objectives: Platelets aggregating at the site of angioplasty, shown to be a potent proliferative stimulus for cultured smooth muscle cells ( SMC), could contribute to proliferation after angioplasty. Methods: SM C were cultivated from human aorta and restenosed coronary lesions as well as from minipig aorta and from normal and post angioplasty corona ry artery segments (n = 6 per source). 3H-thymidine incorporation was used as a measure of proliferation. Results: 3H-thymidine incorporatio n varied greatly after passage 7 in all cell lines, but was significan tly higher in SMC from human coronary restenosed lesions compared to t hose from human aorta and minipig coronary post angioplasty segments i n passage 2 (44 +/- 6.4 x 10(3) cpm/5000 SMC vs 20 +/- 3.9 and 12.1 +/ - 2.1). However, all SMC exhibited a dramatic increase of 3H-incorpora tion after passage 7. Growth factors stimulated 3H-thymidine incorpora tion either dose dependently (PDGF-BB and bFGF) or only very modestly (PDGF-AA, EGF, IGF-1). The most potent stimulation was seen with PDGF- BB, 50 ng/ml, and was 17 +/- 6 % (human restenosed) and 16 +/- 8 % (mi nipig post angioplasty) of the values observed after stimulation with 10 % fetal calf serum. The most effective combination of growth factor s, PDGF-BB (50 ng/ml) + bFGF (20 ng/ml) + IGF-1 (50 ng/ml), produced a 3H-thymidine incorporation of 44 +/- 10 % (human restenosed) and 42 /- 11 % (minipig post angioplasty) of FCS values. Stimulation by isola ted platelets was dose dependent and significantly higher: 75 +/- 19 % and 70 +/- 15 % of FCS values for those SMC. Conclusions: 1) SMC from all sources studied exhibit significant changes of proliferation with increasing passages, excluding the comparability of data obtained wit h cells in different passages. 2) Data obtained with SMC from any sour ce might not apply for SMC from human coronary restenosed lesions. 3) Currently tested growth factors do not fully account for the prolifera tive effect of platelets on cultured SMC.