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EXPERIMENTAL STUDY

Time courses of apoptosis and cell proliferation and their relationship to arterial remodeling and restenosis after angioplasty in an atherosclerotic rabbit model

Eric Durand, MD^*, Ziad Mallat, MD, PhD, Faouzi Addad, MD^*, Françoise Vilde, MD^*, Michel Desnos, MD^*, Claude Guérot, MD^*, Alain Tedgui, PhD and Antoine Lafont, MD, PhD^*,*

^* INSERM EMI-U 00-16 Paris, France
INSERM U 541, Paris, France

Manuscript received December 7, 2000; revised manuscript received February 13, 2002, accepted February 27, 2002.

^* Reprint requests and correspondence: Dr. Antoine Lafont, Cardiology Department, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75340 Paris Cedex 07, France.
antoine.lafont{at}egp.ap-hop-paris.fr

OBJECTIVES: We sought to evaluate whether cellular mass changes (including apoptosis and proliferation) after arterial injury could interact with restenosis and arterial remodeling.

BACKGROUND: The mechanisms controlling arterial remodeling after angioplasty remain poorly understood. Apoptosis and cell proliferation have been previously described after balloon angioplasty. However, their importance in the occurrence of arterial remodeling and restenosis is unknown.

METHODS: Atherosclerosis was induced in 48 femoral arteries of New Zealand White rabbits by air-desiccation and a high-cholesterol diet. One month later, angioplasty was performed in 40 arteries. Apoptosis, cell proliferation, residual stenosis and arterial remodeling were evaluated at 2 h and 3, 7, 14, 21 and 28 days after angioplasty.

RESULTS: Cell proliferation and apoptosis profiles were similar, but the peak in cell proliferation occurred approximately four days earlier than the peak in apoptosis in the neointima and media. Apoptosis density was positively correlated with arterial remodeling in the neointima and media (r = 0.69, p = 0.005 and r = 0.50, p = 0.05, respectively). Moreover, residual stenosis was inversely correlated with apoptosis density in the neointima and media (r = –0.62, p = 0.008 and r = –0.52, p = 0.04, respectively). In contrast, cell proliferation was independent of restenosis and arterial remodeling.

CONCLUSIONS: In this model, cell proliferation preceded apoptosis throughout the four weeks after angioplasty. Apoptosis was inversely correlated with restenosis. Interestingly, apoptosis was also related to enlargement remodeling after balloon angioplasty.

Abbreviations and Acronyms   DNA   deoxyribonucleic acid   PARP-1   poly (ADP-ribose) polymerase-1   SMC   smooth muscle cell   TUNEL   terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling

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