Human Apolipoprotein A-I Exerts a Prophylactic Effect on High-Fat Diet-Induced Atherosclerosis via Inflammation Inhibition in a Rabbit Model

Acta Biochim Biophys Sin (Shanghai). 2017 Feb 6;49(2):149-158. doi: 10.1093/abbs/gmw128.

Abstract

Apolipoprotein A-I (apoA-I) is the major functional protein fraction of high-density lipoprotein. The prophylactic effect and mechanism of human apoA-I on atherosclerosis (AS) were investigated in a high-fat diet-induced AS rabbit model. The rabbits were injected with apoA-I once a week while fed high-fat diet for 20 weeks. Our results showed that apoA-I could raise the serum level of high-density lipoprotein-cholesterol and reduce those of lipid total cholesterol, triglyceride, and low-density lipoprotein-cholesterol in AS rabbits. Decreased aortic plaque area and aortic injury degree were also observed by Oil Red O staining and HE staining in apoA-I-treated high-fat diet-induced AS rabbits. Further study elucidated that apoA-I could down-regulate the expression of some inflammatory mediators including intercellular adhesion molecule type 1, vascular adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-6 (IL-6), and C-reactive protein in serum and aorta of AS rabbits. In addition, real-time quantitative RT-PCR analyses showed that the apoA-I infusions decreased the mRNA levels of two pro-inflammatory molecules, i.e. nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2), in aorta of AS rabbits, which was associated with a concomitant reduction in endothelial VCAM-1 and IL-6 mRNA transcription. Together, our results support the atheroprotective and prophylactic role of apoA-I in vivo, and this activity may be correlated with its anti-inflammatory effect.

Keywords: apolipoprotein A-I; atherosclerosis; high-density lipoprotein; high-fat diet; inflammation.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Apolipoprotein A-I / administration & dosage
  • Apolipoprotein A-I / pharmacology*
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Atherosclerosis / prevention & control*
  • C-Reactive Protein / metabolism
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cyclooxygenase 2 / blood
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / drug effects
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism*
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • NF-kappa B / blood
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / prevention & control
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / blood
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • APOA1 protein, human
  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Inflammation Mediators
  • Interleukin-6
  • NF-kappa B
  • Triglycerides
  • Vascular Cell Adhesion Molecule-1
  • C-Reactive Protein
  • Cholesterol
  • Cyclooxygenase 2