Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Molecular Pathways of Vulnerability Carotid Plaques at Risk for Ischemic Stroke: A Narrative Review

Giuseppe Miceli
ORCID logo ,
Maria Grazia Basso
,
Chiara Pintus
,
Andrea Roberta Pennacchio
ORCID logo ,
Elena Cocciola
,
Mariagiovanna Cuffaro
,
Martina Profita
,
Giuliana Rizzo
,
Antonino Tuttolomondo
*
Version 1 : Received: 28 February 2024 / Approved: 29 February 2024 / Online: 29 February 2024 (10:54:27 CET)

A peer-reviewed article of this Preprint also exists.

Miceli, G.; Basso, M.G.; Pintus, C.; Pennacchio, A.R.; Cocciola, E.; Cuffaro, M.; Profita, M.; Rizzo, G.; Tuttolomondo, A. Molecular Pathways of Vulnerable Carotid Plaques at Risk of Ischemic Stroke: A Narrative Review. Int. J. Mol. Sci. 2024, 25, 4351. Miceli, G.; Basso, M.G.; Pintus, C.; Pennacchio, A.R.; Cocciola, E.; Cuffaro, M.; Profita, M.; Rizzo, G.; Tuttolomondo, A. Molecular Pathways of Vulnerable Carotid Plaques at Risk of Ischemic Stroke: A Narrative Review. Int. J. Mol. Sci. 2024, 25, 4351.

Abstract

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

Keywords

carotid plaque; stroke; vulnerability; inflammation

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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