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Vascular Proteomics Reveal Novel Proteins Involved in SMC Phenotypic Change: OLR1 as a SMC Receptor Regulating Proliferation and Inflammatory Response.

Kang DH, Choi M, Chang S, Lee MY, Lee DJ, Choi K, Park J, Han EC, Hwang D, Kwon K, Jo H, Choi C, Kang SW - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science and Research Center for Cell Homeostasis, Ewha Womans University, Seoul 120-750, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Increased expression of PKACA and PTPε in human carotid arterial sections with atherosclerotic lesions.Immunohistochemistry was performed using the paraffin-embedded tissue sections of human carotid arteries with thickened intimal lesions (Origin Technologies, Rockville, MD, USA). The indicated proteins were stained with specific immunohistochemistry-compatible antibodies. Frozen sections of normal peripheral arteries were stained for control. The 3’,3’-diaminobenzidine (DAB)-stained images are obtained from 5 patient carotid tissue sections and quantified with the HistoFAXS Tissue Analysis System (TissueGnostics, USA). The expression level is shown as a fold increase of DAB intensities in patient samples versus that in normal vessel. A representative image with patient identification number is shown. The letter “L” indicates the vascular lumen.
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pone.0133845.g005: Increased expression of PKACA and PTPε in human carotid arterial sections with atherosclerotic lesions.Immunohistochemistry was performed using the paraffin-embedded tissue sections of human carotid arteries with thickened intimal lesions (Origin Technologies, Rockville, MD, USA). The indicated proteins were stained with specific immunohistochemistry-compatible antibodies. Frozen sections of normal peripheral arteries were stained for control. The 3’,3’-diaminobenzidine (DAB)-stained images are obtained from 5 patient carotid tissue sections and quantified with the HistoFAXS Tissue Analysis System (TissueGnostics, USA). The expression level is shown as a fold increase of DAB intensities in patient samples versus that in normal vessel. A representative image with patient identification number is shown. The letter “L” indicates the vascular lumen.

Mentions: To elicit a relevance to human vascular disease, we performed immunohistochemistry (IHC) using carotid arterial sections of human patients with atherosclerotic lesion (Fig 5 and S5 Fig). The levels of two of the validated proteins (PKACA and PTPε) were increased in the atherosclerotic lesions by 1.7- and 1.8-fold than those of normal vessel, respectively. This result confirms that our proteomics screening using a balloon-injured rat model elicited the human-relevant atherosclerosis target proteins.


Vascular Proteomics Reveal Novel Proteins Involved in SMC Phenotypic Change: OLR1 as a SMC Receptor Regulating Proliferation and Inflammatory Response.

Kang DH, Choi M, Chang S, Lee MY, Lee DJ, Choi K, Park J, Han EC, Hwang D, Kwon K, Jo H, Choi C, Kang SW - PLoS ONE (2015)

Increased expression of PKACA and PTPε in human carotid arterial sections with atherosclerotic lesions.Immunohistochemistry was performed using the paraffin-embedded tissue sections of human carotid arteries with thickened intimal lesions (Origin Technologies, Rockville, MD, USA). The indicated proteins were stained with specific immunohistochemistry-compatible antibodies. Frozen sections of normal peripheral arteries were stained for control. The 3’,3’-diaminobenzidine (DAB)-stained images are obtained from 5 patient carotid tissue sections and quantified with the HistoFAXS Tissue Analysis System (TissueGnostics, USA). The expression level is shown as a fold increase of DAB intensities in patient samples versus that in normal vessel. A representative image with patient identification number is shown. The letter “L” indicates the vascular lumen.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548952&req=5

pone.0133845.g005: Increased expression of PKACA and PTPε in human carotid arterial sections with atherosclerotic lesions.Immunohistochemistry was performed using the paraffin-embedded tissue sections of human carotid arteries with thickened intimal lesions (Origin Technologies, Rockville, MD, USA). The indicated proteins were stained with specific immunohistochemistry-compatible antibodies. Frozen sections of normal peripheral arteries were stained for control. The 3’,3’-diaminobenzidine (DAB)-stained images are obtained from 5 patient carotid tissue sections and quantified with the HistoFAXS Tissue Analysis System (TissueGnostics, USA). The expression level is shown as a fold increase of DAB intensities in patient samples versus that in normal vessel. A representative image with patient identification number is shown. The letter “L” indicates the vascular lumen.
Mentions: To elicit a relevance to human vascular disease, we performed immunohistochemistry (IHC) using carotid arterial sections of human patients with atherosclerotic lesion (Fig 5 and S5 Fig). The levels of two of the validated proteins (PKACA and PTPε) were increased in the atherosclerotic lesions by 1.7- and 1.8-fold than those of normal vessel, respectively. This result confirms that our proteomics screening using a balloon-injured rat model elicited the human-relevant atherosclerosis target proteins.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science and Research Center for Cell Homeostasis, Ewha Womans University, Seoul 120-750, Korea.

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.

No MeSH data available.


Related in: MedlinePlus