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卵磷脂胆固醇酰基转移酶(LCAT)水平升高与冠状动脉粥样斑块负担减少有关。

Elevated level of lecithin:cholesterol acyltransferase (LCAT) is associated with reduced coronary atheroma burden.

机构信息

Montreal Heart Institute, Montreal, Canada; Université de Montréal, Montreal, Canada; Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland; University Hospital Zurich, Zurich, Switzerland.

Montreal Heart Institute, Montreal, Canada; Université de Montréal, Montreal, Canada.

出版信息

Atherosclerosis. 2018 Sep;276:131-139. doi: 10.1016/j.atherosclerosis.2018.07.025. Epub 2018 Jul 19.

Abstract

BACKGROUND AND AIMS

Lecithin:cholesterol acyltransferase (LCAT), a key enzyme in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT), has been associated with atheroprotection. However, its relation to plaque characteristics has not been confirmed to date. We aimed to determine the relationship between plasma LCAT mass concentration and plaque burden in a multi-center imaging study.

METHODS

Two hundred sixty-seven patients with angiographically proven coronary artery disease (CAD) underwent intravascular ultrasonography (IVUS) imaging. Ninety-six patients without CAD served as controls for biochemistry assessments.

RESULTS

Plasma LCAT mass concentration was higher in CAD patients as compared to controls (8.94 ± 2.51 μg/mL vs. 7.89 ± 2.99 μg/mL, p = 0.003), while cholesterol esterification rate (CER) was downregulated (253.6 ± 83.9 μM/2 h vs. 315.3 ± 115.0 μM/2 h, p<0.0001). Both parameters correlated inversely with total atheroma volume (r = -0.14, p = 0.027 and r = -0.14, p = 0.024, respectively), while only LCAT mass was found to be a significant predictor of atheroma volume (β-coefficient -0.18, p = 0.0047) when tested in a stepwise linear regression model against known CAD risk factors as predictor variables. Accordingly, patients with LCAT mass in the highest quartile had significantly less atheroma burden than those in the lower quartiles (39.7 ± 10.7% vs. 45.4 ± 10.4%, p = 0.0014 for highest vs. lowest quartile of LCAT mass).

CONCLUSIONS

Plasma LCAT mass concentration is upregulated in CAD patients and inversely related to plaque volume, suggesting atheroprotective effects. LCAT mass concentration outperformed LCAT activity in risk prediction models for atheroma burden, suggesting that LCAT mass is a key variable in atheroprotection. Further studies assessing LCAT as a therapeutic target in cardiovascular disease are warranted.

摘要

背景与目的

卵磷脂胆固醇酰基转移酶(LCAT)是高密度脂蛋白(HDL)代谢和胆固醇逆转运(RCT)的关键酶,与动脉粥样硬化保护有关。然而,其与斑块特征的关系尚未得到证实。我们旨在通过多中心影像学研究确定血浆 LCAT 质量浓度与斑块负担之间的关系。

方法

267 例经血管造影证实的冠心病(CAD)患者接受血管内超声(IVUS)成像。96 例无 CAD 的患者作为生化评估的对照组。

结果

与对照组相比,CAD 患者的血浆 LCAT 质量浓度更高(8.94±2.51μg/mL 比 7.89±2.99μg/mL,p=0.003),而胆固醇酯化率(CER)下调(253.6±83.9μM/2h 比 315.3±115.0μM/2h,p<0.0001)。这两个参数与总动脉粥样硬化体积呈负相关(r=-0.14,p=0.027 和 r=-0.14,p=0.024),而仅 LCAT 质量被发现是动脉粥样硬化体积的一个显著预测因子(β系数-0.18,p=0.0047),当在逐步线性回归模型中针对已知的 CAD 危险因素作为预测变量进行测试时。因此,LCAT 质量浓度最高四分位数的患者的动脉粥样硬化负担明显低于最低四分位数的患者(39.7±10.7%比 45.4±10.4%,p=0.0014,最高四分位数与最低四分位数的 LCAT 质量)。

结论

CAD 患者的血浆 LCAT 质量浓度升高,与斑块体积呈负相关,提示具有动脉粥样硬化保护作用。LCAT 质量浓度在动脉粥样硬化负担的风险预测模型中优于 LCAT 活性,表明 LCAT 质量是动脉粥样硬化保护的关键变量。需要进一步研究评估 LCAT 作为心血管疾病的治疗靶点。

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