Search for Reliable Circulating Biomarkers to Predict Carotid Plaque Vulnerability

Núria Puig, Elena Jiménez-Xarrié, Pol Camps-Renom, Sonia Benitez, Núria Puig, Elena Jiménez-Xarrié, Pol Camps-Renom, Sonia Benitez

Abstract

Atherosclerosis is responsible for 20% of ischemic strokes, and the plaques from the internal carotid artery the most frequently involved. Lipoproteins play a key role in carotid atherosclerosis since lipid accumulation contributes to plaque progression and chronic inflammation, both factors leading to plaque vulnerability. Carotid revascularization to prevent future vascular events is reasonable in some patients with high-grade carotid stenosis. However, the degree of stenosis alone is not sufficient to decide upon the best clinical management in some situations. In this context, it is essential to further characterize plaque vulnerability, according to specific characteristics (lipid-rich core, fibrous cap thinning, intraplaque hemorrhage). Although these features can be partly detected by imaging techniques, identifying carotid plaque vulnerability is still challenging. Therefore, the study of circulating biomarkers could provide adjunctive criteria to predict the risk of atherothrombotic stroke. In this regard, several molecules have been found altered, but reliable biomarkers have not been clearly established yet. The current review discusses the concept of vulnerable carotid plaque, and collects existing information about putative circulating biomarkers, being particularly focused on lipid-related and inflammatory molecules.

Keywords: atherothrombotic stroke; biomarkers; carotid atherosclerosis; inflammation; ischemic stroke; lipids; lipoproteins; plaque vulnerability.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Progression of carotid plaque leading to ischemic stroke. Atherosclerosis in the carotid artery is the main cause of atherothrombotic ischemic stroke. Atherosclerosis may develop for years without symptoms for as long as the plaque remains stable. (a) When the mechanisms counteracting inflammation are overwhelmed, the balance to inflammatory processes is favored, leading to necrosis and release of inflammatory mediators and proteolytic enzymes that degrade the fibrous cap. The plaque then becomes unstable. (b) The unstable atherosclerotic plaques may break and then coagulation is triggered, eventually leading to thrombosis and brain ischemic events (c).
Figure 2
Figure 2
Presence of circulating biomarkers in patients with carotid atherosclerosis. Some molecules in the plasma may be indicative of susceptibility to develop atherosclerosis because of their involvement in the origin and destabilization of atherosclerotic plaque, in carotid as well as in other arteries. LDL and modified LDL may play a key role in this regard by first entering the subendothelial space, where they are presumably further modified, and then promoting foam cell formation and inducing an inflammatory response. Eventually, this phenomenon contributes to plaque vulnerability and to the release into the circulation of inflammatory mediators and highly modified LDL, thereby increasing their plasma concentration, particularly in symptomatic patients. In asymptomatic patients, the concentration of some biomarkers may be higher in high-risk vulnerable patients, because their carotid plaques release part of the lesion-related molecules into the circulation or because they have increased levels of certain molecules (as modified forms of LDL) that are involved in triggering plaque progression.
Figure 3
Figure 3
Levels of biomarkers in patients with carotid atherosclerosis and risk of atherothrombotic stroke.

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