Identification Markers of Carotid Vulnerable Plaques: An Update

Abstract

Vulnerable plaques have been a hot topic in the field of stroke and carotid atherosclerosis. Currently, risk stratification and intervention of carotid plaques are guided by the degree of luminal stenosis. Recently, it has been recognized that the vulnerability of plaques may contribute to the risk of stroke. Some classical interventions, such as carotid endarterectomy, significantly reduce the risk of stroke in symptomatic patients with severe carotid stenosis, while for asymptomatic patients, clinically silent plaques with rupture tendency may expose them to the risk of cerebrovascular events. Early identification of vulnerable plaques contributes to lowering the risk of cerebrovascular events. Previously, the identification of vulnerable plaques was commonly based on imaging technologies at the macroscopic level. Recently, some microscopic molecules pertaining to vulnerable plaques have emerged, and could be potential biomarkers or therapeutic targets. This review aimed to update the previous summarization of vulnerable plaques and identify vulnerable plaques at the microscopic and macroscopic levels.

Inflammation, Microcalcification, and Increased Expression of Osteopontin Are Histological Hallmarks of Plaque Vulnerability in Patients with Advanced Carotid Artery Stenosis

“…Although the precise sequence of lesion progression leading to plaque vulnerability is poorly elucidated, the morphological signs of instability as a potential indicator of stroke risk are well known. This hallmark includes a large lipid core, macrophage-mediated inflammatory changes, intraplaque neoangiogenesis/hemorrhage, ulceration, and microcalcification [ 25 ]. In this context, histological identification of these signs in endarterectomy specimens may provide valuable data concerning underlying plaque morphologies and should guide the treatment strategy to prevent further cerebral events.…”

“…Tomas et al, in 159 carotid specimens obtained by endarterectomy, identified an altered metabolomic signature of unstable carotid plaques, comprising increased glycolysis and amino acid utilization along with low fatty-acid oxidation. A series of pro-inflammatory cytokines, like interleukins IL-1b, IL-6, IL-15, IL-17, and IL-18, are abundantly expressed in homogenates of the cluster characterized by the signature mentioned above [ 25 , 30 ]. Chemokines synthesized by MFs, like monocyte chemoattractant protein-1 (MCP-1) and MF inflammatory protein-1b (MIP-1b) were also up-regulated in unstable vs. stable plaques [ 30 ].…”

Higher Leukocyte Count Is Associated with Lower Presence of Carotid Lipid-Rich Necrotic Core: A Sub-Study in the Plaque at RISK (PARISK) Study

“…Finally, a future prospective study should, next to the leukocyte differential count and other inflammatory biomarkers, at least include carotid MRI and ideally one or several forms of imaging parameters that could detect plaque inflammation, in particular positron emission tomography (PET) CT or dynamic contrast enhanced (DCE-)MRI. The need for more research into plaque vulnerability through these new techniques was recently stressed in a review by Wang et al [ 35 ]. For future research into dynamic MRI techniques, the assistance of deep learning methods has been suggested to aid the determination of plaque vulnerability [ 36 ].…”

Role of Preoperative Ultrasound Shear-Wave Elastography and Radiofrequency-Based Arterial Wall Tracking in Assessing the Vulnerability of Carotid Plaques: Preliminary Results

“…Nevertheless, current clinical practice suggests that not all "high-degree" carotid stenosis have the same risk of cerebrovascular events, and this risk particularly is linked to the morphology and to the composition of the carotid plaque, which define the plaque itself as "vulnerable" or "stable" [22]. Since "vulnerable" plaques have been associated with an increased risk of stroke [23], the preoperative identification of vulnerable lesions is crucial for a proper stratification of the operative risk, with a view to providing a stronger justification for the surgical treatment. Currently, the identification of plaque vulnerability features can only be performed with certainty through histological examination after the surgical removal of the plaque [4].…”