A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps

Proceedings of the National Academy of Sciences of the United States of America - Tập 103 Số 40 - Trang 14678-14683 - 2006
Yuliya Vengrenyuk1, Stéphane Carlier2,3, Savvas Xanthos4, Luís Cardoso5, Peter Ganatos4, Renu Virmani6, Shmuel Einav7,8, Lane Gilchrist9, Sheldon Weinbaum5,4
1Department of Biomedical Engineering, City College of New York, Convent Avenue and 138th Street, New York, NY 10031, USA.
2Columbia University Medical Center and Cardiovascular Research Foundation, New York, NY 10027;
3Hart- en vaatziekten
4Mechanical Engineering, and
5Departments of Biomedical Engineering
6CVPath, International Registry of Pathology, Gaithersburg, MD 20878;
7Stony Brook University, Stony Brook, NY 11794; and
8Tel Aviv University, Tel Aviv 69978, Israel
9**Chemical Engineering, City College of New York, New York, NY 10031;

Tóm tắt

In this article, we advance a hypothesis for the rupture of thin fibrous cap atheroma, namely that minute (10-μm-diameter) cellular-level microcalcifications in the cap, which heretofore have gone undetected because they lie below the visibility of current in vivo imaging techniques, cause local stress concentrations that lead to interfacial debonding. New theoretical solutions are presented for the local stress concentration around these minute spherical inclusions that predict a nearly 2-fold increase in interfacial stress that is relatively insensitive to the location of the hypothesized microinclusions in the cap. To experimentally confirm the existence of the hypothesized cellular-level microcalcifications, we examined autopsy specimens of coronary atheromatous lesions using in vitro imaging techniques whose resolution far exceeds conventional magnetic resonance imaging, intravascular ultrasound, and optical coherence tomography approaches. These high-resolution imaging modalities, which include confocal microscopy with calcium-specific staining and micro-computed tomography imaging, provide images of cellular-level calcifications within the cap proper. As anticipated, the minute inclusions in the cap are very rare compared with the numerous calcified macrophages observed in the necrotic core. Our mathematical model predicts that inclusions located in an area of high circumferential stress (>300 kPa) in the cap can intensify this stress to nearly 600 kPa when the cap thickness is <65 μm. The most likely candidates for the inclusions are either calcified macrophages or smooth muscle cells that have undergone apoptosis.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 103 Số 40

14678-14683

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