Thin-capped atheromata with reduced collagen content in pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress

Konstantinos C. Koskinas, Galina K. Sukhova, Aaron B. Baker, Michail I. Papafaklis, Yiannis S. Chatzizisis, Ahmet U. Coskun, Thibaut Quillard, Michael Jonas, Charles Maynard, Antonios P. Antoniadis, Guo Ping Shi, Peter Libby, Elazer R. Edelman, Charles L. Feldman, Peter H. Stone

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Objective-The mechanisms promoting the focal formation of rupture-prone coronary plaques in vivo remain incompletely understood. This study tested the hypothesis that coronary regions exposed to low endothelial shear stress (ESS) favor subsequent development of collagen-poor, thin-capped plaques. Approach and Results-Coronary angiography and 3-vessel intravascular ultrasound were serially performed at 5 consecutive time points in vivo in 5 diabetic, hypercholesterolemic pigs. ESS was calculated along the course of each artery with computational fluid dynamics at all 5 time points. At follow-up, 184 arterial segments with previously identified in vivo ESS underwent histopathologic analysis. Compared with other plaque types, eccentric thin-capped atheromata developed more in segments that experienced lower ESS during their evolution. Compared with lesions with higher preceding ESS, segments persistently exposed to low ESS (<1.2 Pa) exhibited reduced intimal smooth muscle cell content; marked intimal smooth muscle cell phenotypic modulation; attenuated procollagen-I gene expression; increased gene and protein expression of the interstitial collagenases matrix-metalloproteinase-1, -8, -13, and -14; increased collagenolytic activity; reduced collagen content; and marked thinning of the fibrous cap. Conclusions-Eccentric thin-capped atheromata, lesions particularly prone to rupture, form more frequently in coronary regions exposed to low ESS throughout their evolution. By promoting an imbalance of attenuated synthesis and augmented collagen breakdown, low ESS favors the focal evolution of early lesions toward plaques with reduced collagen content and thin fibrous caps-2 critical determinants of coronary plaque vulnerability.

Original languageEnglish (US)
Pages (from-to)1494-1504
Number of pages11
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number7
DOIs
StatePublished - Jul 2013

Keywords

  • Atherosclerosis
  • Collagen
  • Endothelial shear stress
  • Metalloproteinases
  • Natural history

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Koskinas, K. C., Sukhova, G. K., Baker, A. B., Papafaklis, M. I., Chatzizisis, Y. S., Coskun, A. U., Quillard, T., Jonas, M., Maynard, C., Antoniadis, A. P., Shi, G. P., Libby, P., Edelman, E. R., Feldman, C. L., & Stone, P. H. (2013). Thin-capped atheromata with reduced collagen content in pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress. Arteriosclerosis, Thrombosis, and Vascular Biology, 33(7), 1494-1504. https://doi.org/10.1161/ATVBAHA.112.300827