title: Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ.
abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease.
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Beihai
authors.initials: B
authors.lastname: Ge
authors.affiliation: Department of Cardiology, China Three Gorges University, Yichang 433000, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Medical College, Shihezi University, PR China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Qian
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China. Electronic address: xmguo@tjh.tjmu.edu.cn.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Guo
mesh_terms: D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: ATP binding cassette transporter A1; ATP binding cassette transporter G1; Mitofusin 2; Peroxisome proliferator-activated receptor γ; Scavenger receptor class B type I