Circulating ANGPTL3/8 Concentrations Are Associated With an Atherogenic Lipoprotein Profile and Increased CHD Risk in Swedish Population-Based Studies.
Karin Leander, Yan Q Chen, Max Vikström, Angela Silveira, Rachel M Fisher, Robert J Konrad, Ferdinand M van 't Hooft
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引用次数: 0
Abstract
Background: Binding of ANGPTL (angiopoietin-like protein)-3 to ANGPTL8 generates a protein complex (ANGPTL3/8) that strongly inhibits LPL (lipoprotein lipase) activity, as compared with ANGPTL3 alone, suggesting that ANGPTL3/8 concentrations are critical for the regulation of circulation lipoprotein concentrations and subsequent increased coronary heart disease (CHD) risk. To test this hypothesis in humans, we evaluated the associations of circulating free ANGPTL3 and ANGPTL3/8 complex concentrations with lipoprotein concentrations and CHD risk in 2 prospective cohort studies.
Methods: Fasting blood samples were obtained in conjunction with the baseline evaluation of 9479 subjects from 2 population-based Swedish cohorts of middle-aged men and women. Standard biochemical blood analyses, including all lipid/lipoprotein measurements, were performed in these samples at baseline. Additional serum samples were stored at -80 °C and used at a later stage for ANGPTL3 and ANGPTL3/8 concentration measurements. Information about incident CHD was obtained for both cohorts by matching to the Swedish National Patient Register and the Cause of Death Register.
Results: ANGPTL3 concentrations showed modest, positive associations with all lipoprotein concentrations but were not associated with CHD risk. In contrast, ANGPTL3/8 concentrations were associated in both cohorts with an atherogenic lipoprotein profile (characterized by increased triglyceride and LDL [low-density lipoprotein] concentrations and reduced HDL [high-density lipoprotein] concentrations). In the combined cohort, ANGPTL3/8 was associated with increased CHD risk. Hazard ratio per 1 SD increase was 1.10 (95% CI, 1.03-1.17) after adjustment for age, sex, cohort, smoking, and hypertension.
Conclusions: Elevated concentrations of ANGPTL3/8, but not ANGPTL3, are associated with an atherogenic lipoprotein profile and increased CHD risk in humans.
期刊介绍：
The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA).
The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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