Differences between the Molecular Mechanisms Underlying Ruptured and Non-Ruptured Carotid Plaques, and the Significance of ABCA1

Abstract

Background and Purpose Carotid plaques are a strong risk factor for ischemic stroke, and plaque rupture poses an even higher risk. Although many studies have investigated the pathogenic mechanisms of carotid plaque formation, few have studied the differences in molecular mechanisms underlying the rupture and non-rupture of carotid plaques. In addition, since early diagnosis and treatment of carotid plaque rupture are critical for the prevention of ischemic stroke, many studies have sought to identify the important target molecules involved in the rupture. However, a target molecule critical in symptomatic ruptured plaques is yet to be identified.Methods A total of 79 carotid plaques were consecutively collected, and microscopically divided into ruptured and non-ruptured groups. Quantitative polymerase chain reaction array, proteomics, and immunohistochemistry were performed to compare the differences in molecular mechanisms between ruptured and non-ruptured plaques. Enzyme-linked immunosorbent assay was used to measure the differences in ATP-binding cassette subfamily A member 1 (ABCA1) levels in the serum.Results The expression of several mRNAs and proteins, including ABCA1, was higher in ruptured plaques than non-ruptured plaques. In contrast, the expression of other proteins, including β-actin, was lower in ruptured plaques than non-ruptured plaques. The increased expression of ABCA1 was consistent across several experiments, ABCA1 was positive only in the serum of patients with symptomatic ruptured plaques.Conclusions This study introduces a plausible molecular mechanism underlying carotid plaque rupture, suggesting that ABCA1 plays a role in symptomatic rupture. Further study of ABCA1 is needed to confirm this hypothesis.

Evidence of association of circulating epigenetic-sensitive biomarkers with suspected coronary heart disease evaluated by Cardiac Computed Tomography

“…Regarding the molecular analysis of ABCA1, literature data reported significant associations of dysregulation of this cholesterol transporter with the atherosclerotic process and CHD [47–52]. Indeed, an involvement of ABCA1 has been demonstrated in the formation and composition of carotid atherosclerotic plaques with an upregulation of ABCA1 levels between atherosclerotic and healthy tissues [51], as well as the significance of this biomarker in plaque rupture [52]. In our study we have shown from peripheral blood sample that ABCA1 mRNA was up-regulated in patients with CHD underwent to CCT, suggesting a possible implication in disease diagnosis and high-risk plaque detection.…”

DNA Methylation and SNPs of ABCA1 Gene Promoter Affect Gene Expression and Involve in the Pathological Mechanism of Ischemic Stroke

“…Rupture of atherosclerotic plaque will increase the risk of IS. Heo et al found that the mRNA expression of ABCA1 and protein in ruptured plaque was signi cantly higher than unruptured plaque, which proved that ABCA1 was involved in plaque rupture process (Heo SH et al, 2018). ABCA1 can inhibit the secretion of in ammatory cytokines to mediate immune response and play an anti atherosclerotic role.…”

Imaging retinal microvascular manifestations of carotid artery disease in older adults: from diagnosis of ocular complications to understanding microvascular contributions to cognitive impairment

“…In a recent study, RNA expression, proteomic and IHC analysis found that ABCA1 CD44, KLF2, PLIN2, ferritin, ACTB, CAIX, and ENO1 protein levels were significantly higher in ruptured plaques than in non-ruptured plaques. Bioinformatic analysis suggested that only ABCA1 has a preventive role in carotid plaque rupture and atherosclerosis progression during the inflammatory reaction [49]. There are many IHC markers (CD3, CD68, CD31, CD34, MMP9) expression in special localization in the plaque, which were suspected to be useful to identify the high-risk plaques [50][51][52].…”