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. 2024 Feb 8;119(2):193–213. doi: 10.1007/s00395-024-01033-5

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — The interplay between the main cap components: collagen, macrophages, and microcalcifications and essential reviews discussing the influence of SMC’s and T cells on these components [16, 65, 74, 118, 137, 231, 243, 269]. A Macrophages influence the collagenous matrix by secretion of cytokines, ECM components, AGEs, and proteases. Furthermore, integrins detect matrix properties and regulate processes of macrophage biology, by which the collagenous matrix properties, thus, modulate cell functionality. B Collagen serves as a scaffold for microcalcification formation and collagen type, cross-linking and degradation can affect the formation of microcalcifications. Furthermore, microcalcifications themselves affect collagen architecture. C Macrophages release cytokines, osteogenic factors, proteases, and EVs that can alter calcification formation. In addition, macrophage apoptosis contributes to microcalcification formation. Microcalcifications, in turn, modulate macrophage functionality by promoting release of pro- or anti-inflammatory factors.

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