Apoptosis bcl-2 and nitrotyrosine expression in an angioplasty-restenosis rabbit: an experimental model.
Apoptosis has been suggested to have an important role in the pathogenesis of restenosis in addition to cell migration and proliferation. The aim of the present study was to investigate in an experimental in vivo model the occurrence of apoptosis postangioplasty and its relation to bcl-2 and peroxynitrite detection. Eighteen hypercholesterolemic rabbits underwent transluminal angioplasty of the right iliac artery. The rabbits were sacrificed on the 1st, 2nd, 3rd, 7th, 15th, and 28th day postangioplasty (3 animals per time point) and both the angioplasted and non-injured arteries were studied. Apoptosis was assessed by the terminal uridine nick-end labeling method (TUNEL). Bcl-2 and peroxynitrite were detected by immunochemistry using anti-bcl-2 and anti-nitrotyrosine antibodies. In the angioplasted arteries the number of apoptotic cells was <or=1% of the total cell population in both media and neointima at any of the postangioplasty time points examined. Bcl-2 and nitrotyrosines were detected at all time points in the angioplasted arteries (vs. non-injured, P<0.001), showed similar localization and had the same peaks of expression both in the media (7th day: Bcl-2 66% and nitrotyrosines 74%) and neointima (15th day: Bcl-2 67% and nitrotyrosines 61%). In this experimental model we observed low apoptotic rates while bcl-2 and peroxynitrite products were detected. We can hypothesize that the detection of nitrotyrosines is related with reduced levels of nitric oxide resulting in increased expression of the bcl-2, preventing thus cell death due to either apoptosis or necrosis. Further studies are needed in order to elucidate their role in the restenosis process.
Department of Cardiac Surgery, University of Athens School of Medicine, Attikon Hospital Center, Georgiou Sisini 31, 11528 Athens, Greece. toumpoul@otenet.gr <toumpoul@otenet.gr>
Ioannis K
IK
Toumpoulis
Vassiliki D
VD
Malamou-Mitsi
Lampros K
LK
Michalis
Christos
C
Katsouras
Georgia
G
Gloustianou
Dimitrios
D
Galaris
Mary
M
Bai
Dimitrios
D
Vardakas
Niki J
NJ
Agnantis
Dimitrios A
DA
Sideris
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002465:Cell Movement; D049109:Cell Proliferation; D007083:Iliac Artery; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000293:injuries* / Q000378:metabolism* / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011817:Rabbits; D012008:Recurrence; D018709:Statistics, Nonparametric; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine