Circulating Biomarkers Reflecting Destabilization Mechanisms of Coronary Artery Plaques: Are We Looking for the Impossible?

Abstract

Despite significant strides to mitigate the complications of acute coronary syndrome (ACS), this clinical entity still represents a major global health burden. It has so far been well-established that most of the plaques leading to ACS are not a result of gradual narrowing of the vessel lumen, but rather a result of sudden disruption of vulnerable atherosclerotic plaques. As most of the developed imaging modalities for vulnerable plaque detection are invasive, multiple biomarkers were proposed to identify their presence. Owing to the pivotal role of lipids and inflammation in the pathophysiology of atherosclerosis, most of the biomarkers originated from one of those processes, whereas recent advancements in molecular sciences shed light on the use of microRNAs. Yet, at present there are no clinically implemented biomarkers or any other method for that matter that could non-invasively, yet reliably, diagnose the vulnerable plaque. Hence, in this review we summarized the available knowledge regarding the pathophysiology of plaque instability, the current evidence on potential biomarkers associated with plaque destabilization and finally, we discussed if search for biomarkers could one day bring us to non-invasive, cost-effective, yet valid way of diagnosing the vulnerable, rupture-prone coronary artery plaques.

Keywords: acute coronary syndrome; atherosclerosis; biomarkers; myocardial infarction; plaque erosion; plaque rupture; vulnerable plaque.

Figure 1

Circulating biomarkers of vulnerable plaques and their interplay in the intima of the coronary artery. LDL migrates from blood to plaque, where it goes through series of modifications. By binding to LOX-1, oxLDL activates and upregulates the production of MMP-9, whereas shedding of the LOX-1 receptor allows its peripheral blood detection. The complex between NGAL and MMP-9 results in extended proteolytic activity of MMP-9. Lp-PLA2 is responsible for hydrolysis of ox-PL on LDL particles and subsequent release of proinflammatory lipids. MMP-9: Matrix metalloproteinase-9; NGAL: Neutrophil gelatinase-associated lipocalin; sLOX-1: soluble part of the Lectin-like oxidized low-density lipoprotein receptor-1; Ox-LDL: oxidized low-density lipoprotein; Ox-PL: oxidized phospholipids; Lp-PLA2: lipoprotein-associated phospholipase A2; LDL(-): electronegative low-density lipoprotein; LDL: low-density lipoprotein; miRNA-100: microRNA-100; lncRNA: long non-coding RNA.