Associations of ANGPTL proteins and complexes with progression of coronary artery calcification and coronary events

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis Pub Date : 2025-08-13 DOI:10.1016/j.atherosclerosis.2025.120485

Günther Silbernagel , Halle Higbie , Tanja Meininger , Deven Lemen , Hongxia Li , Yan Q. Chen , Yi Wen , Eugene Y. Zhen , Yue-Wei Qian , Polina Korovianskaia , Hans J. Trampisch , Hubert Scharnagl , Winfried März , Andreas Stang , Raimund Erbel , Robert J. Konrad , Börge Schmidt

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引用次数: 0

Abstract

Background and aims

Angiopoietin-like protein 8 (ANGPTL8) forms complexes with ANGPTL3 and ANGPTL4 to regulate lipoprotein lipase (LPL) activity, and decreased LPL activity is an established cardiovascular risk factor. Serum levels of ANGPTL4/8 and C-terminal domain-containing ANGPTL4 (CD-ANGPTL4) are positively associated with cardiovascular death, however, the underlying mechanisms remain incompletely understood. The present study investigated relationships of ANGPTL3, ANGPTL3/8, CD-ANGPTL4, and ANGPTL4/8 with coronary artery calcification (CAC) progression (using Agatston scores) and incident coronary events.

Methods

ANGPTL3, ANGPTL3/8, CD-ANGPTL4, and ANGPTL4/8, were measured using dedicated immunoassays in participants of the Heinz Nixdorf Recall (HNR) study, an unselected, population-based cohort of subjects free from cardiovascular disease at baseline. CAC measurements were performed at baseline and after 5 years in 2887 participants, and there was follow-up for coronary events (median duration 18.8 years).

Results

Median Agatston scores increased over 5 years from 6.70 (t₀) to 24.75 (t₁), and 315 participants experienced a coronary event. Concentrations of ANGPTL3 and ANGPTL3/8 were not associated with Agatston score progression. ANGPTL3 was associated with incident coronary events, whereas ANGPTL3/8 was not. In contrast, CD-ANGPTL4 and ANGPTL4/8 were positively associated with both Agatston score progression and incident coronary events.

Conclusions

Associations of ANGPTL3 and ANGPTL3/8 with coronary atherosclerosis progression and incident coronary events were inconsistent, while CD-ANGPTL4 and ANGPTL4/8 were associated with both coronary atherosclerosis progression and incident coronary events. Associations of ANGPTL4/8 and CD-ANGPTL4 with cardiovascular events may reflect progression of coronary atherosclerosis conferred by diabetes, inflammation, or the potential intrinsic effects of CD-ANGPTL4 and ANGPTL4/8.

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ANGPTL蛋白和复合物与冠状动脉钙化和冠状动脉事件进展的关系

背景与目的血管生成素样蛋白8 （ANGPTL8）与ANGPTL3和ANGPTL4形成复合物，调节脂蛋白脂肪酶（LPL）活性，LPL活性降低是心血管疾病的危险因素。血清ANGPTL4/8和含有c末端结构域的ANGPTL4 （CD-ANGPTL4）水平与心血管死亡呈正相关，然而，其潜在机制尚不完全清楚。本研究探讨了ANGPTL3、ANGPTL3/8、CD-ANGPTL4和ANGPTL4/8与冠状动脉钙化（CAC）进展（使用Agatston评分）和冠心病事件的关系。方法在Heinz Nixdorf Recall （HNR）研究的参与者中使用专用免疫分析法测量sangptl3、ANGPTL3/8、CD-ANGPTL4和ANGPTL4/8，该研究是一项未选择的、基于人群的基线无心血管疾病受试者队列。2887名参与者在基线和5年后进行了CAC测量，并对冠状动脉事件进行了随访（中位持续时间18.8年）。结果中位Agatston评分在5年内从6.70 （t1）增加到24.75 (t1)， 315名参与者经历了冠状动脉事件。ANGPTL3和ANGPTL3/8的浓度与Agatston评分进展无关。ANGPTL3与冠心病事件相关，而ANGPTL3/8与冠心病事件无关。相比之下，CD-ANGPTL4和ANGPTL4/8与Agatston评分进展和冠心病事件均呈正相关。结论ANGPTL3和ANGPTL3/8与冠状动脉粥样硬化进展和冠脉事件的相关性不一致，而CD-ANGPTL4和ANGPTL4/8与冠状动脉粥样硬化进展和冠脉事件均相关。ANGPTL4/8和CD-ANGPTL4与心血管事件的关联可能反映了由糖尿病、炎症或CD-ANGPTL4和ANGPTL4/8的潜在内在效应引起的冠状动脉粥样硬化的进展。

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来源期刊

Atherosclerosis 医学-外周血管病

CiteScore

9.80

自引率

3.80%

发文量

1269

审稿时长

36 days

期刊介绍： Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.