Circulating ANGPTL3 and ANGPTL4 levels predict coronary artery atherosclerosis severity

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Abstract

Background

We investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis.

Methods

A total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits.

Results

According to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively.

Conclusions

Increased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12944-021-01580-z.

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Most cited references 38

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Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Karen Courville, Sergei Ermakov, Maheswar Satpathy … (2015)

The Lancet, 385(9963), 117-171

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A review on coronary artery disease, its risk factors, and therapeutics

Arup Kr. Malakar, Debashree Choudhury, Binata Halder … (2019)

Coronary artery disease (CAD) is one of the major cardiovascular diseases affecting the global human population. This disease has been proved to be the major cause of death in both the developed and developing countries. Lifestyle, environmental factors, and genetic factors pose as risk factors for the development of cardiovascular disease. The prevalence of risk factors among healthy individuals elucidates the probable occurrence of CAD in near future. Genome-wide association studies have suggested the association of chromosome 9p21.3 in the premature onset of CAD. The risk factors of CAD include diabetes mellitus, hypertension, smoking, hyperlipidemia, obesity, homocystinuria, and psychosocial stress. The eradication and management of CAD has been established through extensive studies and trials. Antiplatelet agents, nitrates, β-blockers, calcium antagonists, and ranolazine are some of the few therapeutic agents used for the relief of symptomatic angina associated with CAD.

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Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease.

Frederick E Dewey, Viktoria Gusarova, Richard Dunbar … (2017)

Background Loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease. Methods We sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss-of-function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow-up studies involving 23,317 case patients and 107,166 controls from four population studies. We also tested the effects of a human monoclonal antibody, evinacumab, against Angptl3 in dyslipidemic mice and against ANGPTL3 in healthy human volunteers with elevated levels of triglycerides or LDL cholesterol. Results In the DiscovEHR study, participants with heterozygous loss-of-function variants in ANGPTL3 had significantly lower serum levels of triglycerides, HDL cholesterol, and LDL cholesterol than participants without these variants. Loss-of-function variants were found in 0.33% of case patients with coronary artery disease and in 0.45% of controls (adjusted odds ratio, 0.59; 95% confidence interval, 0.41 to 0.85; P=0.004). These results were confirmed in the follow-up studies. In dyslipidemic mice, inhibition of Angptl3 with evinacumab resulted in a greater decrease in atherosclerotic lesion area and necrotic content than a control antibody. In humans, evinacumab caused a dose-dependent placebo-adjusted reduction in fasting triglyceride levels of up to 76% and LDL cholesterol levels of up to 23%. Conclusions Genetic and therapeutic antagonism of ANGPTL3 in humans and of Angptl3 in mice was associated with decreased levels of all three major lipid fractions and decreased odds of atherosclerotic cardiovascular disease. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT01749878 .).

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Author and article information

Contributors

Ting Sun:

ORCID: http://orcid.org/0000-0003-3747-1810

beibeisun2008@163.com

Changqian Wang: changqianwang@hotmail.com

Junfeng Zhang: jfzhang_dr@163.com

Journal

Journal ID (nlm-ta): Lipids Health Dis

Journal ID (iso-abbrev): Lipids Health Dis

Title: Lipids in Health and Disease

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-511X

Publication date (Electronic): 6 November 2021

Publication date PMC-release: 6 November 2021

Publication date Collection: 2021

Volume: 20

Electronic Location Identifier: 154

Affiliations

GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Cardiology, , Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, ; Shanghai, 200025 China

Author information

Ting Sun http://orcid.org/0000-0003-3747-1810

Article

Publisher ID: 1580

DOI: 10.1186/s12944-021-01580-z

PMC ID: 8571829

PubMed ID: 34742313

SO-VID: 1a133990-1fce-4550-8c36-47c50e73255c

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 26 August 2021

Date accepted : 12 October 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81770505

Award Recipient : Ting Sun

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ScienceOpen disciplines: Biochemistry

Keywords: angptl3,angptl4,coronary atherosclerosis,predictors

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ScienceOpen disciplines: Biochemistry

Keywords: angptl3, angptl4, coronary atherosclerosis, predictors

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Circulating ANGPTL3 and ANGPTL4 levels predict coronary artery atherosclerosis severity

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Abstract

Background

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Results

Conclusions

Supplementary Information

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Journal of Circulating Biomarkers

Most cited references 38

Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

A review on coronary artery disease, its risk factors, and therapeutics

Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease.

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Cited by 8

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