Human apolipoprotein A-I exerts a prophylactic effect on high-fat diet-induced atherosclerosis via inflammation inhibition in a rabbit model

摘要

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 lowdensity 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 dietinduced 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 proinflammatory 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.