Vascular proteomics reveal novel proteins involved in SMC phenotypic change: OLR1 as a SMC receptor regulating proliferation and inflammatory response

Dong Hoon Kang, Mina Choi, Soyoung Chang, Min Young Lee, Doo Jae Lee, Kyungsun Choi, Junseong Park, Eun Chun Han, Daehee Hwang, Kihwan Kwon, Hanjoong Jo, Chulhee Choi, Sang Won Kang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 epitheliallike 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-êB activation and by assisting the PDGFinduced 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.

Original languageEnglish
Article numbere0133845
JournalPLoS ONE
Volume10
Issue number8
DOIs
StatePublished - 25 Aug 2015

Fingerprint

Dive into the research topics of 'Vascular proteomics reveal novel proteins involved in SMC phenotypic change: OLR1 as a SMC receptor regulating proliferation and inflammatory response'. Together they form a unique fingerprint.

Cite this