Protein kinase C pathway and proliferative responses of aged and young rat vascular smooth muscle cells.
Alterations of vascular smooth muscle cell (VSMC) proliferation have been implicated in the age-dependent susceptibility to atherosclerosis. Although it is known that protein kinase C (PKC) is involved in the mechanism of VSMC proliferation, there are no data on the possible involvement of PKC in disregulating VSMC proliferation in aged vascular cells. We evaluated the proliferative pattern, the PKC responsiveness and the effect of phorbol ester (PMA) treatment on vascular cell growth and cell cycle distribution in VSMCs from young and aged rats. The proliferative response was significantly higher in aged than in young cells after serum stimulation (7.5 vs. 2.8 x 10(4), 18 vs. 12 x 10(4), 26 vs. 22 x 10(4) cells/well, aged vs. young at days 2, 4, 6; P < 0.005). On the contrary, aged cells showed a significant inhibition of DNA synthesis at 48 h incubation with PMA concentrations of 1, 10, 100 nM (-47%, -53%, -58%, respectively) compared with controls (fetal calf serum 0.5%) and cell count (average decrease: -38% from 48 h to 96 h) after treatment with PMA 10 nM. The opposite was observed in young cells on [3H]thymidine incorporation with PMA 1, 10, 100 nM (+52%, +100%, +121%, respectively and cell count (average increase +55% from 48 h to 96 h). In addition, inhibition of the cell cycle from G1 to the S phase and reduction of PKC translocation in aged VSMC were observed. Alterations of PKC function could be involved in the disregulation of aged VSMC proliferation, which seems to characterize the increased susceptibility to atherosclerosis.
Porreca
E
E
Istituto di Patologia Speciale Medica, Università G. D'Annunzio, Facoltà di Medicina e Chirurgia, Chieti, Italy.
Ciccarelli
R
R
Di Febbo
C
C
Cuccurullo
F
F
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate