Mechanisms of fibrous cap formation in atherosclerosis

Front Cardiovasc Med. 2023 Aug 21:10:1254114. doi: 10.3389/fcvm.2023.1254114. eCollection 2023.

Abstract

The fibrous cap is formed by smooth muscle cells that accumulate beneath the plaque endothelium. Cap rupture is the main cause of coronary thrombosis, leading to infarction and sudden cardiac death. Therefore, the qualities of the cap are primary determinants of the clinical outcome of coronary and carotid atherosclerosis. In this mini-review, we discuss current knowledge about the formation of the fibrous cap, including cell recruitment, clonal expansion, and central molecular signaling pathways. We also examine the differences between mouse and human fibrous caps and explore the impact of anti-atherosclerotic therapies on the state of the fibrous cap. We propose that the cap should be understood as a neo-media to substitute for the original media that becomes separated from the surface endothelium during atherogenesis and that embryonic pathways involved in the development of the arteria media contribute to cap formation.

Keywords: arterial media development; atherosclerosis; clonal expansion; fibrous cap; neomedia; plaque rupture; smooth muscle cells.

Publication types

  • Review

Grants and funding

LA-H is supported by a grant from the Danish Cardiovascular Academy (PD2Y-2022003-DCA), JA-J by a grant from the Aarhus University Research Foundation (Starting Grant, AUFF-E-201 9-7-23) and JB by grants from the Novo Nordisk Foundation (NNF17OC0030688), Ministerio de Ciencia e Innovación with cofunding from the European Regional Development Fund (PID2019-108568RB-I00), and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 866240). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MICIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).