Min Zhang1, Guo-Jun Zhao2, Feng Yao1, Xiao-Dan Xia1, Duo Gong1, Zhen-Wang Zhao1, Ling-Yan Chen1, Xi-Long Zheng3, Xiao-Er Tang4, Chao-Ke Tang5. 1. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medicine Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China. 2. Department of Histology and Embryology, Guilin Medical University, No. 1 Zhiyuan Road, Guilin, Guangxi 541100, China. 3. Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr. N.W., Calgary, Alberta T2N 4N1, Canada. 4. Department of Pathophysiology, Shaoyang University, Shaoyang, Hunan 422000, China. Electronic address: tangxiaoer19800505@tom.com. 5. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medicine Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China. Electronic address: tangchaoke@qq.com.
Abstract
BACKGROUND AND AIMS: ApoA-1 binding protein (AIBP) is a secreted protein that interacts with apoA-I and accelerates cholesterol efflux from cells. We have recently reported that AIBP promotes apoA-1 binding to ABCA1 in the macrophage cell membrane, partially through 115-123 amino acids. However, the effects of AIBP on the development of atherosclerosis in vivo remain unknown. METHODS: ApoE-/- mice with established atherosclerotic plaques were infected with rAAV-AIBP or rAAV-AIBP(Δ115-123), respectively. RESULTS: AIBP-treated mice showed reduction of atherosclerotic lesion formation, increase in circulating HDL levels and enhancement of reverse cholesterol transport to the plasma, liver, and feces. AIBP increased ABCA1 protein levels in aorta and peritoneal macrophages. Furthermore, AIBP could diminish atherosclerotic plaque macrophage content and the expression of chemotaxis-related factors. In addition, AIBP prevented macrophage inflammation by inactivating NF-κB and promoted the expression of M2 markers like Mrc-1 and Arg-1. However, lack of 115-123 amino acids of AIBP(Δ115-123) had no such preventive effects on the progression of atherosclerosis. CONCLUSIONS: Our observations demonstrate that AIBP inhibits atherosclerosis progression and suggest that it may be an effective target for prevention of atherosclerosis.
BACKGROUND AND AIMS: ApoA-1 binding protein (AIBP) is a secreted protein that interacts with apoA-I and accelerates cholesterol efflux from cells. We have recently reported that AIBP promotes apoA-1 binding to ABCA1 in the macrophage cell membrane, partially through 115-123 amino acids. However, the effects of AIBP on the development of atherosclerosis in vivo remain unknown. METHODS:ApoE-/- mice with established atherosclerotic plaques were infected with rAAV-AIBP or rAAV-AIBP(Δ115-123), respectively. RESULTS:AIBP-treated mice showed reduction of atherosclerotic lesion formation, increase in circulating HDL levels and enhancement of reverse cholesterol transport to the plasma, liver, and feces. AIBP increased ABCA1 protein levels in aorta and peritoneal macrophages. Furthermore, AIBP could diminish atherosclerotic plaque macrophage content and the expression of chemotaxis-related factors. In addition, AIBP prevented macrophage inflammation by inactivating NF-κB and promoted the expression of M2 markers like Mrc-1 and Arg-1. However, lack of 115-123 amino acids of AIBP(Δ115-123) had no such preventive effects on the progression of atherosclerosis. CONCLUSIONS: Our observations demonstrate that AIBP inhibits atherosclerosis progression and suggest that it may be an effective target for prevention of atherosclerosis.
Authors: Soo-Ho Choi; Aaron M Wallace; Dina A Schneider; Elianne Burg; Jungsu Kim; Elena Alekseeva; Niki Dj Ubags; Carlyne D Cool; Longhou Fang; Benjamin T Suratt; Yury I Miller Journal: JCI Insight Date: 2018-08-23
Authors: Hann Low; Nigora Mukhamedova; Luciano Dos Santos Aggum Capettini; Yining Xia; Irena Carmichael; Stephen H Cody; Kevin Huynh; Michael Ditiatkovski; Ryunosuke Ohkawa; Michael Bukrinsky; Peter J Meikle; Soo-Ho Choi; Seth Field; Yury I Miller; Dmitri Sviridov Journal: Arterioscler Thromb Vasc Biol Date: 2020-08-13 Impact factor: 8.311