title: Vascular Proteomics Reveal Novel Proteins Involved in SMC Phenotypic Change: OLR1 as a SMC Receptor Regulating Proliferation and Inflammatory Response.
abstract: Neointimal hyperplasia of vascular smooth muscle cells (VSMC) plays a critical role in atherosclerotic plaque formation and in-stent restenosis, but the underlying mechanisms are still incompletely understood. We performed a proteomics study to identify novel signaling molecules organizing the VSMC hyperplasia. The differential proteomics analysis in a balloon-induced injury model of rat carotid artery revealed that the expressions of 44 proteins are changed within 3 days post injury. The combination of cellular function assays and a protein network analysis further demonstrated that 27 out of 44 proteins constitute key signaling networks orchestrating the phenotypic change of VSMC from contractile to epithelial-like synthetic. Among the list of proteins, the in vivo validation specifically revealed that six proteins (Rab15, ITR, OLR1, PDHβ, PTPε) are positive regulators for VSMC hyperplasia. In particular, the OLR1 played dual roles in the VSMC hyperplasia by directly mediating oxidized LDL-induced monocyte adhesion via NF-κB activation and by assisting the PDGF-induced proliferation/migration. Importantly, OLR1 and PDGFRβ were associated in close proximity in the plasma membrane. Thus, this study elicits the protein network organizing the phenotypic change of VSMC in the vascular injury diseases such as atherosclerosis and discovers OLR1 as a novel molecular link between the proliferative and inflammatory responses of VSMCs.
authors: Department of Life Science and Research Center for Cell Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors: Dong Hoon
authors: DH
authors: Kang
authors: Department of Life Science and Research Center for Cell Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors: Mina
authors: M
authors: Choi
authors: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea.
authors: Soyoung
authors: S
authors: Chang
authors: School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang 790-784, Korea.
authors: Min Young
authors: MY
authors: Lee
authors: Department of Life Science and Research Center for Cell Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors: Doo Jae
authors: DJ
authors: Lee
authors: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea.
authors: Kyungsun
authors: K
authors: Choi
authors: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea.
authors: Junseong
authors: J
authors: Park
authors: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea.
authors: Eun Chun
authors: EC
authors: Han
authors: School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang 790-784, Korea; Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, DGIST, Daegu 711-873, Korea.
authors: Daehee
authors: D
authors: Hwang
authors: Department of Cardiology and College of Medicine, Ewha Womans University, Seoul 120-750, Korea; Global Top5 Research program, Ewha Womans University, Seoul 120-750, Korea.
authors: Kihwan
authors: K
authors: Kwon
authors: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA30322, United States of America.
authors: Hanjoong
authors: H
authors: Jo
authors: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea.
authors: Chulhee
authors: C
authors: Choi
authors: Department of Life Science and Research Center for Cell Homeostasis, Ewha Womans University, Seoul 120-750, Korea; Global Top5 Research program, Ewha Womans University, Seoul 120-750, Korea.
authors: Sang Won
authors: SW
authors: Kang
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology*; D058426:Neointima / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D017207:Rats, Sprague-Dawley; D051131:Receptors, Oxidized LDL / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction; D020298:U937 Cells
chemical_list: C495137:OLR1 protein, human; C495136:OLR1 protein, rat; D010982:Platelet-Derived Growth Factor; D020543:Proteome; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E