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Microcalcifications, Their Genesis, Growth, and Biomechanical Stability in Fibrous Cap Rupture

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Molecular, Cellular, and Tissue Engineering of the Vascular System

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1097))

Abstract

For many decades, cardiovascular calcification has been considered as a passive process, accompanying atheroma progression, correlated with plaque burden, and apparently without a major role on plaque vulnerability. Clinical and pathological analyses have previously focused on the total amount of calcification (calcified area in a whole atheroma cross section) and whether more calcification means higher risk of plaque rupture or not. However, this paradigm has been changing in the last decade or so. Recent research has focused on the presence of microcalcifications (μCalcs) in the atheroma and more importantly on whether clusters of μCalcs are located in the cap of the atheroma. While the vast majority of μCalcs are found in the lipid pool or necrotic core, they are inconsequential to vulnerable plaque. Nevertheless, it has been shown that μCalcs located within the fibrous cap could be numerous and that they behave as an intensifier of the background circumferential stress in the cap. It is now known that such intensifying effect depends on the size and shape of the μCalc as well as the proximity between two or more μCalcs. If μCalcs are located in caps with very low background stress, the increase in stress concentration may not be sufficient to reach the rupture threshold. However, the presence of μCalc(s) in the cap with a background stress of about one fifth to one half the rupture threshold (a stable plaque) will produce a significant increase in local stress, which may exceed the cap rupture threshold and thus transform a non-vulnerable plaque into a vulnerable one. Also, the classic view that treats cardiovascular calcification as a passive process has been challenged, and emerging data suggest that cardiovascular calcification may encompass both passive and active processes. The passive calcification process comprises biochemical factors, specifically circulating nucleating complexes, which would lead to calcification of the atheroma. The active mechanism of atherosclerotic calcification is a cell-mediated process via cell death of macrophages and smooth muscle cells (SMCs) and/or the release of matrix vesicles by SMCs.

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Acknowledgments

This research has been supported by NIH grants 1R01HL136431 and 1SC1DK103362; NSF grants CMMI-1662970, CMMI-1333560, MRI-0723027, and MRI-1229449; and NYS DOH grant C31291GG.

Conflict of Interest The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Biomedical Engineering, The City College of New York, New York, NY, USA

    Luis Cardoso & Sheldon Weinbaum

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  1. Luis Cardoso
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  2. Sheldon Weinbaum
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Correspondence to Luis Cardoso .

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Editors and Affiliations

  1. Department of Biomedical Engineering, The City College of the City University of New York, New York, NY, USA

    Bingmei M. Fu

  2. Department of Mechanical Engineering, Michigan State University, East Lansing, MI, USA

    Neil T. Wright

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Cardoso, L., Weinbaum, S. (2018). Microcalcifications, Their Genesis, Growth, and Biomechanical Stability in Fibrous Cap Rupture. In: Fu, B., Wright, N. (eds) Molecular, Cellular, and Tissue Engineering of the Vascular System. Advances in Experimental Medicine and Biology, vol 1097. Springer, Cham. https://doi.org/10.1007/978-3-319-96445-4_7

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