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

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)...

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Main Authors: Silbernagel, Günther (Author) , Higbie, Halle (Author) , Meininger, Tanja (Author) , Lemen, Deven (Author) , Li, Hongxia (Author) , Chen, Yan Q. (Author) , Wen, Yi (Author) , Zhen, Eugene Y. (Author) , Qian, Yue-Wei (Author) , Korovianskaia, Polina (Author) , Trampisch, Hans J. (Author) , Scharnagl, Hubert (Author) , März, Winfried (Author) , Stang, Andreas (Author) , Erbel, Raimund (Author) , Konrad, Robert J. (Author) , Schmidt, Börge (Author)
Format: Article (Journal)
Language:English
Published: October 2025
In: Atherosclerosis
Year: 2025, Volume: 409, Pages: 1-9
ISSN:1879-1484
DOI:10.1016/j.atherosclerosis.2025.120485
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.atherosclerosis.2025.120485
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0021915025013838
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Author Notes: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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Summary: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.
Item Description:Online verfügbar: 13. August 2025, Artikelversion: 16. August 2025
Gesehen am 18.11.2025
Physical Description:Online Resource
ISSN:1879-1484
DOI:10.1016/j.atherosclerosis.2025.120485

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