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

Abstract

Carotid plaques are a strong risk factor for ischemic stroke, and in terms of plaque rupture, the risk goes even higher. In spite of the significance of carotid plaques, few have studied the differences in molecular mechanisms between ruptured and non-ruptured carotid plaques. Previous studies have focused on identifying the crucial target molecules in ruptured plaques, since early diagnosis and therapy for carotid plaque rupture is important to prevent ischemic stroke. However, critical factors for symptomatic ruptured plaques are yet to be identified. In this study, 79 carotid plaques were collected and microscopically determined as ruptured or non-ruptured plaques. For examination of RNA and protein dynamics in plaques, quantitative polymerase chain reaction (qPCR) array, proteomics, and immunohistochemistry (IHC) were conducted to compare their molecular expression. According to the results, they revealed that levels of several factors, including ATP-binding cassette subfamily A member 1 (ABCA1), were significantly higher in ruptured plaques than in non-ruptured ones. To identify the utility of ABCA1 as a clinical biomarker in carotid rupture, enzyme-linked immunosorbent assay (ELISA) was performed using patients’ sera. The expression of ABCA1 was consistently demonstrated in the serum of patients with symptomatic ruptured plaques, while those with non-ruptured plaques were all negative for ABCA1. Taken together, our results suggest a plausible mechanism involving carotid plaque rupture, and point out ABCA1 as a biomarker for symptomatic carotid plaque rupture.