他汀类药物影响atp结合盒A1膜转运体介导的胆固醇外排能力与类风湿关节炎冠状动脉粥样硬化的关系

IF 4.7 Q2 IMMUNOLOGY
George A. Karpouzas , Bianca Papotti , Sarah R. Ormseth , Marcella Palumbo , Elizabeth Hernandez , Maria Pia Adorni , Francesca Zimetti , Matthew J. Budoff , Nicoletta Ronda
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We here evaluated associations between ABCA1-CEC, coronary atherosclerosis and cardiovascular risk and the influence of statins on those relationships in rheumatoid arthritis (RA).</p></div><div><h3>Methods</h3><p>Evaluation with computed tomography angiography was undertaken in 140 patients and repeated in 99 after 6.9 ± 0.3 years. Events comprising cardiovascular death, acute coronary syndromes, stroke, claudication, revascularization and heart failure were recorded. ABCA1-CEC and ABCG1-CEC were evaluated in J774A.1 macrophages and Chinese hamster ovary (CHO) cells respectively and expressed as percentage of effluxed over total intracellular cholesterol. Covariates in all cardiovascular event risk and plaque outcome models included atherosclerotic cardiovascular disease (ASCVD) risk score and high-density lipoprotein cholesterol.</p></div><div><h3>Results</h3><p>ABCA1-CEC negatively correlated with ABCG1-CEC (r = −0.167, p = 0.049). ABCA1-CEC associated with cardiovascular risk (adjusted hazard ratio 2.05 [95%CI 1.20–3.48] per standard deviation [SD] increment). There was an interaction of ABCA1-CEC with time-varying statin use (p = 0.038) such that current statin use inversely associated with risk only in patients with ABCA1-CEC below the upper tertile. ABCA1-CEC had no main effect on plaque or plaque progression; instead, ABCA1-CEC (per SD) associated with fewer baseline total plaques (adjusted rate ratio [aRR] 0.81, [95%CI 0.65–1.00]), noncalcified plaques (aRR 0.78 [95%CI 0.61–0.98]), and vulnerable low-attenuation plaques (aRR 0.41 [95%CI 0.23–0.74]) in statin users, and more low-attenuation plaques (aRR 1.91 [95%CI 1.18–3.08]) in nonusers (p-for-interaction = 0.018, 0.011, 0.025 and &lt; 0.001 respectively). 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引用次数: 0

摘要

目的胆固醇外排能力(CEC)是高密度脂蛋白(HDL)抗动脉粥样硬化的主要功能。atp结合盒A1 (ABCA1)膜转运体启动胆固醇从动脉巨噬细胞输出到β前HDL颗粒,促进其成熟;反过来,它们通过abcg1介导的输出接受胆固醇。β - HDL成熟受损可能破坏两种转运体的协同功能,并对动脉粥样硬化产生不利影响。他汀类药物对斑块具有全身和局部的动脉粥样硬化保护作用。我们在此评估了ABCA1-CEC、冠状动脉粥样硬化和心血管风险之间的关系,以及他汀类药物对类风湿关节炎(RA)患者这些关系的影响。方法140例患者行ct血管造影评估,99例患者术后6.9±0.3年复查。记录了心血管死亡、急性冠状动脉综合征、中风、跛行、血运重建术和心力衰竭等事件。测定J774A的ABCA1-CEC和ABCG1-CEC。1巨噬细胞和中国仓鼠卵巢(CHO)细胞,并以外排胆固醇占细胞内总胆固醇的百分比表达。所有心血管事件风险和斑块结局模型的协变量包括动脉粥样硬化性心血管疾病(ASCVD)风险评分和高密度脂蛋白胆固醇。结果abca1 - cec与ABCG1-CEC呈负相关(r = - 0.167, p = 0.049)。ABCA1-CEC与心血管风险相关(校正风险比2.05 [95%CI 1.20-3.48] /标准差[SD]增量)。ABCA1-CEC与随时间变化的他汀类药物使用存在相互作用(p = 0.038),因此目前他汀类药物的使用仅在ABCA1-CEC低于上五分位的患者中与风险呈负相关。ABCA1-CEC对斑块或斑块进展无主要影响;相反,ABCA1-CEC(每SD)与他汀类药物使用者较少的基线总斑块(调整比值[aRR] 0.81, [95%CI 0.65-1.00])、非钙化斑块(aRR 0.78 [95%CI 0.61-0.98])和易损性低衰减斑块(aRR 0.41 [95%CI 0.23-0.74])相关,与非他汀类药物使用者较多的低衰减斑块(aRR 1.91 [95%CI 1.18-3.08])相关(相互作用p = 0.018, 0.011, 0.025和<0.001分别)。此外,ABCA1-CEC(每SD)仅在随访期间未暴露于他汀类药物的患者中与更大的部分/完全钙化斑块进展相关(校正优势比3.07 [95%CI 1.20-7.86])(相互作用p = 0.009)。结论在RA患者中,较高的ABCA1-CEC可能反映了动脉粥样硬化状态,与心血管风险增加相关。他汀类药物的使用可能揭示abca1介导的胆固醇外排对斑块形成、进展和心血管风险的保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Statins influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis

Statins influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis

Statins influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis

Statins influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis

Objectives

Cholesterol efflux capacity (CEC) is the main antiatherogenic function of high-density lipoprotein (HDL). ATP-binding-cassette A1 (ABCA1) membrane transporter initiates cholesterol export from arterial macrophages to pre-β HDL particles fostering their maturation; in turn, those accept cholesterol through ABCG1-mediated export. Impaired pre-β HDL maturation may disrupt the collaborative function of the two transporters and adversely affect atherosclerosis. Statins exert atheroprotective functions systemically and locally on plaque. We here evaluated associations between ABCA1-CEC, coronary atherosclerosis and cardiovascular risk and the influence of statins on those relationships in rheumatoid arthritis (RA).

Methods

Evaluation with computed tomography angiography was undertaken in 140 patients and repeated in 99 after 6.9 ± 0.3 years. Events comprising cardiovascular death, acute coronary syndromes, stroke, claudication, revascularization and heart failure were recorded. ABCA1-CEC and ABCG1-CEC were evaluated in J774A.1 macrophages and Chinese hamster ovary (CHO) cells respectively and expressed as percentage of effluxed over total intracellular cholesterol. Covariates in all cardiovascular event risk and plaque outcome models included atherosclerotic cardiovascular disease (ASCVD) risk score and high-density lipoprotein cholesterol.

Results

ABCA1-CEC negatively correlated with ABCG1-CEC (r = −0.167, p = 0.049). ABCA1-CEC associated with cardiovascular risk (adjusted hazard ratio 2.05 [95%CI 1.20–3.48] per standard deviation [SD] increment). There was an interaction of ABCA1-CEC with time-varying statin use (p = 0.038) such that current statin use inversely associated with risk only in patients with ABCA1-CEC below the upper tertile. ABCA1-CEC had no main effect on plaque or plaque progression; instead, ABCA1-CEC (per SD) associated with fewer baseline total plaques (adjusted rate ratio [aRR] 0.81, [95%CI 0.65–1.00]), noncalcified plaques (aRR 0.78 [95%CI 0.61–0.98]), and vulnerable low-attenuation plaques (aRR 0.41 [95%CI 0.23–0.74]) in statin users, and more low-attenuation plaques (aRR 1.91 [95%CI 1.18–3.08]) in nonusers (p-for-interaction = 0.018, 0.011, 0.025 and < 0.001 respectively). Moreover, ABCA1-CEC (per SD) associated with greater partially/fully-calcified plaque progression (adjusted odds ratio 3.07 [95%CI 1.20–7.86]) only in patients not exposed to statins during follow-up (p-for-interaction = 0.009).

Conclusion

In patients with RA, higher ABCA1-CEC may reflect a proatherogenic state, associated with enhanced cardiovascular risk. Statin use may unmask the protective impact of ABCA1-mediated cholesterol efflux on plaque formation, progression and cardiovascular risk.

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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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