Higher circulating levels of ANGPTL8 are associated with body mass index, triglycerides, and endothelial dysfunction in patients with coronary artery disease

Mol Cell Biochem. 2020 Jun;469(1-2):29-39. doi: 10.1007/s11010-020-03725-7. Epub 2020 Apr 1.

Abstract

Bac Coronary artery disease (CAD) is the leading cause of death worldwide and most commonly develops as a result of atherosclerosis. ANGPTL8 is a secreted adipokine that regulates lipid metabolism and is associated with cardiometabolic diseases, including type 2 diabetes and CAD. However, the association between circulating ANGPTL8 levels and CAD is inconsistent among studies and the mechanism by which ANGPTL8 contributes to CAD development remains poorly understood. Here we sought to evaluate the relationship between ANGPTL8 levels and endothelial dysfunction and adipose tissue inflammation in CAD patients. Concentrations of ANGPTL8, adiponectin, TNF-α, IL6, hsCRP, ICAM-1, and VCAM-1 were measured by ELISA in serum samples from 192 CAD patients diagnosed with stenosis > 50% in at least one coronary artery by angiography and 71 individuals with normal heart function. Serum ANGPTL8 levels were significantly higher in CAD patients compared to controls (83.84 ± 23.25 ng/mL vs. 50.45 ± 17.73; p < 0.001), independent of adjustment for age, sex, BMI, smoking and statin use. ANGPTL8 could also differentiate CAD patients from controls with 82.3% specificity and 81.4% sensitivity (p < 0.001). Adiponectin levels were lower in CAD patients, while ICAM-1, VCAM-1, TNF-α, IL6, and hsCRP levels were higher compared to non-CAD controls (all p < 0.001). ANGPTL8 levels were associated with BMI in controls and with BMI, TG, and ICAM-1 in CAD patients. The presence of elevated ANGPTL8 levels in CAD patients and independent association with TG and ICAM-1 suggest a possible role related to endothelial dysfunction in the pathogenesis of atherosclerosis.

Keywords: Betatrophin/lipasin; Cardiovascular disease; Inflammation; Lipid metabolism; Vascular function.

MeSH terms

  • Adiponectin / blood
  • Adipose Tissue / metabolism*
  • Adipose Tissue / physiopathology
  • Aged
  • Angiopoietin-Like Protein 8
  • Angiopoietin-like Proteins / blood*
  • Angiopoietin-like Proteins / genetics
  • Body Mass Index
  • C-Reactive Protein / metabolism
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / physiopathology
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Patients
  • Peptide Hormones / blood*
  • Peptide Hormones / genetics
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vascular Diseases / metabolism

Substances

  • ANGPTL8 protein, human
  • Adiponectin
  • Angiopoietin-Like Protein 8
  • Angiopoietin-like Proteins
  • ICAM1 protein, human
  • Interleukin-6
  • Peptide Hormones
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein