Dynamic changes of ATP binding cassette transporter A1 expression in perihematomal tissue of mouse cerebral hemorrhage model induced by collagenase / 国际脑血管病杂志

Objective To investigate the ATP binding cassette transporter A1 (ABCA1) expression in perihematomal tissue of mouse cerebral hemorrhage model induced by collagenase. Methods Stereotactic injection of type Ⅳ collagenase was used to induce a model of caudate putamen intracerebral hemorrhage in mice. The behavioral scores were use to assess neurological deficits at 24 h, 48 h and 72 h after model making. Neisserian staining was used to detect the morphology of neurons around hematomas.Immunohistochemical staining and Western blot analysis were used to detect the expression of ABCA1 around hematomas. Results Nissl bodies reduction, atrophy, necrosis of perihematomal neurons were observed and aggravated over time. Immunohistochemical staining and Western blot analysis showed that the expression level of ABCA1 in the perihematomal tissue was significantly higher than that in the sham operation group (all P < 0. 05), and the expression level increased significantly with time (all P < 0. 05 ).Conclusion ABCA1 was up-regulated after cerebral hemorrhage, suggesting that it might be involved in the pathological process of cerebral hemorrhage.

Role of ABCA1 in angiotensin Ⅱ-induced cholesterol accumulation in podocytes / 中华肾脏病杂志

Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) on the expression of ATP-binding cassette transporter A1(ABCA1) in Ang Ⅱ-infused rat model and cultured human podocytes,and to explore the role of ABCA1 in Ang Ⅱ-induced cholesterol accumulation of podocytes.Methods Twelve Wistar rats were randomly subjected to normal saline infusion,or Ang Ⅱ infusion at 400 ng· kg-1 · min-1 (via subcutaneous osmotic minipumps) for 8 weeks.The expression of glomerular ABCA1 was analyzed by Western blotting and real-time fluorescent quantitative PCR.In vitro,conditionally immortalized human podocytes were divided into normal group,Ang Ⅱ group,Ang Ⅱ + scrambled siRNA group,Ang Ⅱ + ABCA1 siRNA group.The expression of podocyte ABCA1 was assessed by immunofluorescence,Western blotting and real-time fluorescent quantitative PCR.Oil Red 0 staining was used to observe the lipid droplets in podocytes and cholesterol efflux assay kit was used to measure the cholesterol efflux rate of podocytes.Fluorescein isothiocyanate (FITC)-conjugated phalloidin was used to observe the podocyte cytoskeleton.Results In vivo,compared with normal group,the protein and mRNA expression of glomerular ABCA1 in Ang Ⅱ-infused rats were decreased (P ＜ 0.05).In vitro,ABCA1 was distributed in the cytomembrane of podocytes,and compared with normal group,Ang Ⅱ treatment down-regulated the expression of ABCA1 (P ＜ 0.05).Increased lipid droplets,decreased cholesterol efflux and cytoskeletal rearrangement were observed in Ang Ⅱ-treated podocytes.When compared to Ang Ⅱ group,podocytes stimulated by Ang Ⅱ and then transfected with ABCA1 siRNA had lower expression level of ABCA1 mRNA and protein (all P ＜ 0.05).More lipid droplets and lower cholesterol efflux rate could be observed in Ang Ⅱ +ABCA1 siRNA group (P＜ 0.05).Conclusion The reduced expression of ABCA1 may be involved in Ang Ⅱ-induced cholesterol accumulation in podocytes.

Association of R219K polymorphism in the ABCA1 gene with ischemic stroke in a Chinese Han population / 国际脑血管病杂志

Objective To investigate the correlation between R219K (rs2230806 G/A) polymorphism in the ATP binding cassette transporter (ABC) A1 gene and ischemic stroke in a Chinese Han population. Methods A total of 360 patients with ischemic stroke and 358 healthy subjects were selected using a case-control study design. The patients with ischemic stroke were redivided into either a large artery atherosclerosis (LAA) group or a smal artery occlusion (SAO) group according to the TOAST criteria. Polymerase chain reaction-restriction fragment length polymorphism analysis and direct sequencing method were used to detect R219K (rs2230806 G/A) polymorphism in the ABCA1 gene. Results Using GG genotype as a reference, the AA genotype reduced the risk of ischemic stroke by 65% (odds ratio [OR] 0. 35, 95%confidence interval [CI] 0. 23 - 0. 55; P 0. 05). AA genotype was enable to increase the high-density lipoprotein cholesterol levels of the patient group (OR 0. 35, 95% CI 0. 28 - 0. 42; P < 0. 001) and the control group (OR 0. 19, 95% CI 0. 14 - 0. 23; P < 0. 001) significantly, while it did not have significant correlation with the low-density lipoprotein cholesterol, total cholesterol, and triglyceride. Conclusions R219K (rs2230806 G/A) polymorphism in the ABCA1 gene may be associated with the reduced predisposition of ischemic stroke in a Chinese Han population, especialy LAA. The A alele may be a hereditary protective factor; its mechanism may be associated with the increase of high-density lipoprotein cholesterol levels.

Effects of R219K polymorphism of ATP-binding cassette transporter 1 gene on serum lipids ratios induced by a high-carbohydrate and low-fat diet in healthy youth

BACKGROUND: Diets are the important players in regulating plasma lipid profiles. And the R219K polymorphism at the gene of ATP-binding cassette transporter 1(ABCA1) was reported to be associated with the profiles. However, no efforts have been made to investigate the changes of lipid profiles after a high-carbohydrate and low-fat diet in different subjects with different genotypes of this polymorphism. This study was to evaluate the effects of ABCA1 R219K polymorphism on serum lipid and apolipoprotein (apo) ratios induced by a high-carbohydrate/low-fat (high-CHO) diet. After a washout diet of 54.1% carbohydrate for 7 days, 56 healthy young subjects (22.89 ± 1.80 years old) were given a high-CHO diet of 70.1% carbohydrate for 6 days. Height, weight, waist circumference, hip circumference, glucose (Glu), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoA-1 and apoB-100 were measured on the 1st, 8th and 14th days of this study. Body mass index (BMI), waist-to-hip ratios (WHR), log(TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoA-1/apoB-100 were calculated. ABCA1 R219K was analyzed by a PCR-RFLP method. RESULTS: The results indicate that the male subjects of all the genotypes had higher WHR than their female counterparts on the 1st, 8th and 14th days of this study. The male K carriers had higher log(TG/HDL-C) and TC/HDL-C than the female carriers on the 1st and 14th days, and higher LDL-C/HDL-C on the 14th day. When compared with that on the 8th day, TC/HDL-C was decreased regardless of the genotypes and genders on the 14th day. Log(TG/HDL-C) was increased in the males with the RR genotype and the female K carriers. Lowered BMI, Glu and LDL-C/HDL-C were found in the male K carriers, but only lowered BMI in the female K carriers and only lowered LDL-C/HDL-C in the females with the RR genotype. CONCLUSIONS: These results suggest that ABCA1 R219K polymorphism is associated differently in males and females with elevated log(TG/HDL-C) and decreased LDL-C/HDL-C induced by the high-CHO diet.

A case of Tangier disease with two novel mutations in the ATP-binding cassette transporter A1 gene / 대한내과학회지

Tangier disease (TD) is a rare autosomal recessive disorder of lipoprotein metabolism characterized by extremely low levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I resulting in accumulation of cholesterol esters in various organs. TD is caused by mutations in the ATP-binding cassette transporter A1 (ABCA1) gene. Here, we present the first case report of a Korean patient with TD. A 45-year-old man had corneal opacity, intestinal mucosa abnormalities, and extremely low levels of HDL-C (1.8 mg/dL) and apo A-I (T (p.G1050X) nonsense mutation and c.3202C>T (p.R1068C) missense mutation. The c.3202C>T mutation was not found in 192 normal control alleles.

High glucose, unsaturated and saturated fatty acids differentially regulate expression of ATP-binding cassette transporters ABCA1 and ABCG1 in human macrophages

The ATP-binding cassette transporters ABCA1 and ABCG1 are highly expressed in macrophage-derived foam cells and promote reverse cholesterol efflux via biogenesis of high-density lipoproteins. The aim of this study was to analyze the direct effects of bioactive factors related to the metabolic syndrome on macrophage transcript levels of all 47 human ABC transporters. Using in vitro M-CSF predifferentiated macrophages and TaqMan low density arrays we could show that linoleic acid, palmitic acid, and high glucose levels have a major impact on ABCA1 and ABCG1 expression but do not strongly affect most other human ABC transporters. In Western blot experiments we demonstrate that ABCA1 and ABCG1 protein levels are synchronously suppressed by high glucose levels and the omega6-unsaturated fatty acid linoleic acid. We conclude that metabolites associated with the metabolic syndrome enhance the formation of atherosclerotic lesions by diminishing the reverse cholesterol transport function of ABCA1 and ABCG1.

Effect of statins on ABCA1 gene expression in neurons and astrocytes / 西安交通大学学报(医学版)

Objective To observe the effects of statins on ATP-binding cassette transporter 1(ABCA1) gene expression in neurons and astrocytes.Methods Primary human astrocytes and neuron cell line HCN-2 were incubated with simvastatin and pravastatin at different concentrations and under different conditions.Using RNA isolated from the cultured cells,we performed quantitative PCR to measure the ABCA1 gene expression in astrocytes and neurons.The protein expression of ABCA1 was measured by Western blot.Results The two statins significantly decreased the ABCA1 gene and protein expressions.Compared with pravastatin,simvastatin significantly reduced the expression of ABCA1 in neurons and astrocytes by 95% and 75%,respectively(both P