Ke Zhang1, Xiaoling Liu1, Yang Yu1, Tian Luo1, Lin Wang1, Chen Ge1, Xinxin Liu1, Jiantao Song1, Xiancheng Jiang1, Yun Zhang1, Shucun Qin1, Mei Zhang2. 1. From The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, People's Republic of China (K.Z., X.L., L.W., C.G., X.L., J.S., Y.Z., M.Z.); The Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, Shandong, People's Republic of China (Y.Y., T.L., S.Q.); and Department of Cell Biology, State University of New York, Downstate Medical Center, New York (X.J.). 2. From The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, People's Republic of China (K.Z., X.L., L.W., C.G., X.L., J.S., Y.Z., M.Z.); The Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, Shandong, People's Republic of China (Y.Y., T.L., S.Q.); and Department of Cell Biology, State University of New York, Downstate Medical Center, New York (X.J.). daixh@vip.sina.com shucunqin@hotmail.com.
Abstract
OBJECTIVE: Phospholipid transfer protein (PLTP) accelerates the development of atherosclerosis in mouse models. We examined the role of PLTP in atherosclerotic plaque stability. APPROACH AND RESULTS: We prepared apolipoprotein E and PLTP double-knockout (PLTP(-/-)ApoE(-/-)) mice. PLTP deficiency significantly decreased lesion size and reduced monocyte/macrophage infiltration, as well as macrophage apoptosis in lesion areas. Moreover, it increased fibrous content in plaques, which suggests that PLTP may affect atherosclerotic plaque stability. Importantly, PLTP overexpression mediated by adenovirus had the reverse effect. It promoted the accumulation of reactive oxygen species in macrophages, which could lead to cell apoptosis and increased the production of inflammatory cytokines and chemokines. PLTP overexpression could promote receptor-interacting protein 3 recruitment of macrophages in cytoplasm, which could induce reactive oxygen species, thus inducing atherogenesis. CONCLUSIONS: PLTP plays an important role in modulating the stability of atherosclerotic plaques. The receptor-interacting protein 3- reactive oxygen species signal pathway could be involved in this PLTP-mediated process.
OBJECTIVE:Phospholipid transfer protein (PLTP) accelerates the development of atherosclerosis in mouse models. We examined the role of PLTP in atherosclerotic plaque stability. APPROACH AND RESULTS: We prepared apolipoprotein E and PLTP double-knockout (PLTP(-/-)ApoE(-/-)) mice. PLTPdeficiency significantly decreased lesion size and reduced monocyte/macrophage infiltration, as well as macrophage apoptosis in lesion areas. Moreover, it increased fibrous content in plaques, which suggests that PLTP may affect atherosclerotic plaque stability. Importantly, PLTP overexpression mediated by adenovirus had the reverse effect. It promoted the accumulation of reactive oxygen species in macrophages, which could lead to cell apoptosis and increased the production of inflammatory cytokines and chemokines. PLTP overexpression could promote receptor-interacting protein 3 recruitment of macrophages in cytoplasm, which could induce reactive oxygen species, thus inducing atherogenesis. CONCLUSIONS:PLTP plays an important role in modulating the stability of atherosclerotic plaques. The receptor-interacting protein 3- reactive oxygen species signal pathway could be involved in this PLTP-mediated process.
Authors: Sanna Hellberg; Johanna M U Silvola; Max Kiugel; Heidi Liljenbäck; Olli Metsälä; Tapio Viljanen; Jari Metso; Matti Jauhiainen; Pekka Saukko; Pirjo Nuutila; Seppo Ylä-Herttuala; Juhani Knuuti; Anne Roivainen; Antti Saraste Journal: Cardiovasc Diabetol Date: 2016-02-06 Impact factor: 9.951