Proliferative response of human and minipig smooth muscle cells after coronary 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: SMC were cultivated from human aorta and restenosed coronary lesions as well as from minipig aorta and from normal and post angioplasty coronary artery segments (n = 6 per source). 3H-thymidine incorporation was used as a measure of proliferation. Results: 3H-thymidine incorporation varied greatly after passage 7 in all cell lines, but was significantly higher in SMC from human coronary restenosed lesions compared to those from human aorta and minipig coronary post angioplasty segments in 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-incorporation after passage 7. Growth factors stimulated 3H-thymidine incorporation 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 % (minipig post angioplasty) of the values observed after stimulation with 10 % fetal calf serum. The most effective combination of growth factors, 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 isolated 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 with cells in different passages. 2) Data obtained with SMC from any source might not apply for SMC from human coronary restenosed lesions. 3) Currently tested growth factors do not fully account for the proliferative effect of platelets on cultured SMC.