Immune-Mediated Inflammation in Vulnerable Atherosclerotic Plaques

Abstract

Atherosclerosis is a chronic long-lasting vascular disease leading to myocardial infarction and stroke. Vulnerable atherosclerotic (AS) plaques are responsible for these life-threatening clinical endpoints. To more successfully work against atherosclerosis, improvements in early diagnosis and treatment of AS plaque lesions are required. Vulnerable AS plaques are frequently undetectable by conventional imaging because they are non-stenotic. Although blood biomarkers like lipids, C-reactive protein, interleukin-6, troponins, and natriuretic peptides are in pathological ranges, these markers are insufficient in detecting the critical perpetuation of AS anteceding endpoints. Thus, chances to treat the patient in a preventive way are wasted. It is now time to solve this dilemma because clear results indicate a benefit of anti-inflammatory therapy per se without modification of blood lipids (CANTOS Trial, NCT01327846). This fact identifies modulation of immune-mediated inflammation as a new promising point of action for the eradication of fatal atherosclerotic endpoints.

Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability

“…[164]. In addition, modulation of immune-mediated inflammation is a new promising point of action for the eradication of fatal atherosclerotic events [135]. The Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS) trial confirmed that targeting inflammation with interleukin-1β (IL-1 β) inhibition significantly reduces cardiovascular events [165].…”

“…MMPs are involved in various stages of plaque progression that are important to predict future atherothrombotic cardiovascular events [134]. Vulnerable atherosclerotic plaques are responsible for life-threatening clinical endpoints; thus, the best approach for both stroke and myocardial infarction (MI) would be safe diagnosis and knock out of the vulnerable lesion before endpoints occur [135]. Higher markers of matrix remodeling, such as MMP-9 and TIMP-1, were associated with a greater prevalence of carotid stenosis and subclinical atherosclerosis in the internal carotid artery (IC) [136].…”

The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability

“…Increased MMP-9 expression and activity promote ECM degradation, which can enhance inflammatory cell infiltration. Histopathological studies showed that MMP-9 was mostly distributed in the shoulder regions, necrotic core, and the fibrous cap of carotid atherosclerotic plaques [ 53 ] that contained an abundance of inflammatory cells [ 54 ]. The inflammatory cells are the primary source of MMP-9 within the plaque [ 55 ].…”

Early identification of carotid vulnerable plaque in asymptomatic patients

“…Up to 60% of acute myocardial infarction (AMI), sudden cardiac death and stroke are the first manifestations of the disease [13]. Therefore, it is of great significance for early accurate assessment and effective intervention of vulnerable plaques [14]. In addition to the previously studied risk factors for unstable plaque formation such as hypertension, T 2 DM, and lipids, this study find that serum markers MMP-9, LOX-1, and YKL-40 are also independent risks of unstable plaque formation.…”

“…Up to 60% of acute myocardial infarction (AMI), sudden cardiac death and stroke are the first manifestations of the disease [ 13 ]. Therefore, it is of great significance for early accurate assessment and effective intervention of vulnerable plaques [ 14 ].…”