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Abstract. The ATP-binding cassette transporter A1 (ABCA1) is an important effector in the regulation of cholesterol efflux from cells. In this study, we assessed the role of ABCA1 in human carotid atherosclerotic plaques (CAPs). We found that ABCA1 and retinoid X receptor α (RXRα) mRNAs were significantly increased in the atherosclerotic plaques compared to control arteries. The increased ABCA1 mRNA correlated with that of RXRα in plaques. According to the modified American Heart Association plaque classification, atherosclerotic specimens were assigned to three grades, and ABCA1 and RXRα mRNA levels were compared across plaques of different grades. Resultantly, plaques of grade Ⅱ and Ⅲ exhibited higher mRNA levels than grade Ⅰ, but there was no difference in mRNA levels between plaques of grade Ⅱ and Ⅲ. By contrast, ABCA1 and RXRα protein levels were notably reduced in plaques relative to control tissues. Similarly, plaques of grade Ⅱ and Ⅲ exhibited lower ABCA1 and RXRα protein levels than grade Ⅰ, and there was no difference in protein levels between plaques of grade Ⅱ and Ⅲ. Our findings suggest that decreased ABCA1 protein plays a key role in the pathogenesis of CAP; the regulation of ABCA1 may be mediated by RXRα and ABCA1 mRNA levels may serve as an indicator for plaque stability. IntroductionCarotid atherosclerotic plaque (CAP) is a predominant established risk factor for stroke, which is associated with high morbidity and mortality (1). Although the development of carotid plaques is influenced by environmental factors, such as elevated blood pressure and serum lipoprotein abnormalities (2), studies have been increasingly focusing on the genetic causes associated with the formation of atherosclerosis. ATP-binding cassette transporter 1 (ABCA1) has been recognized as a major mediator in the initial step of the reverse cholesterol transport, and was shown to facilitate the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins (apo)A-I and apoE from peripheral cells, resulting in the formation of nascent or pre-high-density lipoprotein (HDL) (3,4). Such a cholesterol efflux process prevents the accumulation of cholesterol or oxidative low-density lipoprotein (LDL) in peripheral cells, including macrophages within the arterial wall and, therefore, reduces the accumulation of atherosclerotic plaque.ABCA1 deficiency was indentified to be responsible for Tangier disease and familial HDL deficiency. These conditions are characterized by low levels of HDL, excessive deposition of cholesteryl esters in tissue macrophages and an increased risk for atherosclerotic disease (5). The underlying mechanism is thought to result from the failure of ABCA1 to transport cholesterol and phospholipids out of cells to form complexes with apolipoproteins to generate HDL (6). The intracellular sterol accumulation and subsequent development of foam cells may, as a result, lead to the atheromatous plaque. Due to its important role in atherosclerosis, increasing attention has been focused on ABCA1, so that therapeutic...

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Objectives After ischemic stroke, microglia will be activated and play a key role in neuroinflammation and the destruction of the blood-brain barrier (BBB), and activated microglia could polarize into pro-inflammation M1 phenotype and anti-inflammation M2 phenotype. Dimethyl malonate (DMM) could reduce reactive oxygen species and we speculate DMM could regulate microglia to protect ischemic brain. MethodsWe used transient middle cerebral artery occlusion (tMCAO) mouse model to simulate ischemic stroke and adult male C57BL/6 mice were used in our study. 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct volume. Evans Blue and Brain water content were used to evaluate the destruction of BBB. We used a five-point scale to assess the neurologic function of mice. Western blot and Immunofluorescence were used to measure microglia, pericytes and the expression of related proteins.Results DMM reduced cerebral infarct volume, Evans blue leakage, brain water content and improved neurologic deficits after tMCAO. The number of activated microglia and M1 microglia were decreased and the number of M2 microglia and pericytes were increased after DMM treatment. The expression of tumor necrosis factor-α was reduced while protein levels of IL-10 and ZO-1 were increased through DMM treatment.Conclusions DMM could regulate activation and polarization of microglia to inhibit neuroinflammation and protect BBB. NeuroReport 32: 1161