CORONARY ARTERY DISEASE
Increased intimal apoptosis in coronary atherosclerotic vessel segments lacking compensatory enlargement
Ali H. M. Hassan, MDa,
Irene M. Lang, MD*,a,
Mihaela Ignatescu, MDa,
Robert Ullrich, MDb,
Diana Bonderman, MDa,
Paul Wexberg, MDa,
Franz Weidinger, MDa and
Helmut D. Glogar, MDa
a Department of Cardiology, University of Vienna, Vienna, Austria
b Department of Pathology, University of Vienna, Vienna, Austria
Manuscript received December 20, 1999;
revised manuscript received May 15, 2001,
accepted July 11, 2001.
* Reprint requests and correspondence: Dr. Irene M. Lang, Division of Cardiology, Allgemeines Krankenhaus, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria irene.lang{at}univie.ac.at
OBJECTIVES
In a histopathologic study, we assessed the balance of cell proliferation and apoptosis by counting the number of apoptotic and proliferating cell nuclear antigen-positive cells in freshly harvested atherectomy specimens from 34 patients.
BACKGROUND
Remodeling of human coronary arteries is an adaptive process that alters vascular lumen size.
METHODS
Intravascular ultrasound was performed prior to atherectomy. Total vessel area (area within the external elastic lamina [EEL]), lumen area and plaque area were measured at the region of interest (ROI), and at a proximal and distal reference segment, utilizing the formula . Positive arterial remodeling (R+) resulting in luminal expansion was defined as EEL >10%. Absence of remodeling (0 < EEL <10%) and constrictive arterial remodeling ( EEL <0) were considered as neutral remodeling (R0) and negative remodeling (R), respectively.
RESULTS
In R lesions, apoptotic indices (APO) were significantly elevated (17.17 ± 2.19%) compared with R+ lesions (4.89 ± 1.7%; p = 0.0007). In a rabbit iliac percutaneous transluminal coronary angioplasty model intimal apoptosis was increased four weeks after balloon angioplasty injury (APO 8.8 ± 0.03%) compared with contralateral untreated segments (APO 3.0 ± 0.04%, n = 6). Lesions with an EEL/intimal area <3.0 showed significantly more intimal apoptosis than untreated lesions (p = 0.02).
CONCLUSIONS
The data indicate that constrictive remodeling of atherosclerotic coronary lesions is associated with increased apoptosis of intimal cells. We speculate that increased apoptosis is due to extensive plaque healing after episodes of symptomatic or asymptomatic plaque rupture.
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Abbreviations and Acronyms
| | APO | = apoptotic indices | | DCA | = directional coronary atherectomy | | EEL | = external elastic lamina | | IVUS | = intravascular ultrasound | | LA | = lumen area | | m | = mean | | QCA | = quantitative coronary angiography | | ROI | = region of interest | | PA | = plaque area | | PBS | = phosphate-buffered saline | | PCNA | = proliferating cell nuclear antigen | | px | = proximal reference segment | | TUNEL | = TdT-mediated dUTP biotin nick end labeling |
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E. Durand, Z. Mallat, F. Addad, F. Vilde, M. Desnos, C. Guerot, A. Tedgui, and A. Lafont
Time courses of apoptosis and cell proliferation and their relationship to arterial remodeling and restenosis after angioplasty in an atherosclerotic rabbit model
J. Am. Coll. Cardiol.,
May 15, 2002;
39(10):
1680 - 1685.
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