title: Human apolipoprotein A-I exerts a prophylactic effect on high-fat diet-induced atherosclerosis via inflammation inhibition in a rabbit model.
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.
authors.affiliation: Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Li
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shanghai Benemae Pharmaceutical Corporation, Shanghai International Medical Park, Shanghai 201321, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Feng
authors.affiliation: Shanghai RAAS Blood Products Co., Ltd, Shanghai 201401, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lu
authors.affiliation: Shanghai RAAS Blood Products Co., Ltd, Shanghai 201401, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Si
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000494:pharmacology*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D051546:Cyclooxygenase 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000097:blood / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D002097:C-Reactive Protein; D002784:Cholesterol; D051546:Cyclooxygenase 2
keywords: apolipoprotein A-I; atherosclerosis; high-density lipoprotein; high-fat diet; inflammation