[en] In this article, we advance a hypothesis for the rupture of thin fibrous cap atheroma, namely that minute (10-mum-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 microm. The most likely candidates for the inclusions are either calcified macrophages or smooth muscle cells that have undergone apoptosis.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Vengrenyuk, Yuliya; Department of Biomedical Engineering, City College of New York, Convent Avenue and 138th Street, New York, NY 10031, USA
Carlier, Stéphane ; Columbia University Medical Center > Cardiovascular Research Foundation
Xanthos, Savvas; Department of Mechanical Engineering, City College of New York, New York, NY 10031, United States
Cardoso, Luis; Department of Biomedical Engineering, City College of New York, New York, NY 10031, United States
Ganatos, Peter; Department of Mechanical Engineering, City College of New York, New York, NY 10031, United States
Virmani, Renu; CVPath, International Registry of Pathology, Gaithersburg, MD 20878,
Einav, Shmuel; Stony Brook University, Stony Brook, NY 11794, United States ; Tel Aviv University, Tel Aviv 69978, Israel
Gilchrist, Lane; Department of Chemical Engineering, City College of New York, New York, NY 10031, United States
Weinbaum, Sheldon; Department of Biomedical Engineering, City College of New York, New York, NY 10031, United States ; Department of Mechanical Engineering, City College of New York, New York, NY 10031, United States ; Department of Biomedical Engineering, City College of New York, New York, NY 10031, United States
Language :
English
Title :
A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps.
Publication date :
03 October 2006
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
Proceedings of the National Academy of Sciences, United States
Imoto K, Hiro T, Fujii T, Murashige A, Fukumoto Y, Hashimoto G, Okamura T, Yamada J, Mori K, Matsuzaki M (2005) J Am Coll Cardiol 46:1507-1515.
Goodier J (1933) J Trans ASME 55:39-44.
Gent A, Park B (1984) J Mater Sci 19:1947-1956.
Tsutsui S, Saito K (1973) Proc Japan Natl Congr Appl Mech 23:547-560.
Tsuchida E, Togawa S, Nakahara I (1976) Bull JSME 19:838-848.
Nakahara I, Tsuchida E, Takezaki J, Kodama M (1979) in Recent Research on Mechanical Behavior of Solids, ed Miyamoto H (Univ of Tokyo Press, Tokyo), pp 119-138.