Modulation of apoptosis, proliferation, and p27 expression in a porcine coronary angioplasty model.
Smooth muscle cell (SMC) proliferation is a prominent feature of intimal hyperplasia after percutaneous coronary interventions. p27 is a critical regulator of cell proliferation. Our aims were to analyze the time course of p27 expression, Ki67 proliferative index, and apoptosis after angioplasty in the porcine coronary artery. We also investigated the effects of rapamycin--an antiproliferative drug--on these events. The expression of p27 and Ki67, and apoptosis were determined in porcine coronary arteries harvested at timed intervals from 1 h to 28 days after angioplasty. A gradual increase in p27 expression was observed from 7 to 28 days. Ki67 expression peaked by 7-14 days after angioplasty. By 21-28 days, Ki67 expression decreased, while p27 reached maximal levels. An early apoptotic response was found by 6 h, followed by a gradual return to baseline. Rapamycin induced a reduction in Ki67 proliferative index (2 +/- 0.5%) and an increase in apoptosis (7 +/- 1%) versus untreated animals at the 28-day time point (5 +/- 1 and 1 +/- 0.5%, respectively; P < 0.05). In summary, coronary angioplasty induced a rapid apoptotic response, followed by a progressive increase in proliferation. Later on, as p27 expression increased in the vessel wall, cell proliferation decreased. Modulation of cell cycle progression may be a useful therapeutic approach in the treatment of intimal hyperplasia after angioplasty.
Roque
M
M
Cardiovascular Biology Research Laboratory, The Zena and Michael A. Wiener Cardiovascular Institute, New York, NY 10029-6574, USA.
Cordon-Cardo
C
C
Fuster
V
V
Reis
E D
ED
Drobnjak
M
M
Badimon
J J
JJ
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D002455:Cell Division; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D013552:Swine; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27