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Arterioscler Thromb Vasc Biol. 2017 Mar;37(3):495-505. doi: 10.1161/ATVBAHA.116.308455. Epub 2017 Jan 26.

Endosialin Promotes Atherosclerosis Through Phenotypic Remodeling of Vascular Smooth Muscle Cells.

Author information

1
From the Division of Vascular Oncology and Metastasis (Z.H., T.R., C.K., C.M., S.S.K., C.K., C.S., M.W., S.A., H.G.A.) and Small Animal Imaging (V.E.), German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany; Institute of Pathology, Technical University Munich, Germany (C.M.); Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim (CBTM), Heidelberg University, Germany (S.S.K., M.W., H.G.A.); and German Cancer Consortium, Heidelberg, Germany (H.G.A.).
2
From the Division of Vascular Oncology and Metastasis (Z.H., T.R., C.K., C.M., S.S.K., C.K., C.S., M.W., S.A., H.G.A.) and Small Animal Imaging (V.E.), German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany; Institute of Pathology, Technical University Munich, Germany (C.M.); Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim (CBTM), Heidelberg University, Germany (S.S.K., M.W., H.G.A.); and German Cancer Consortium, Heidelberg, Germany (H.G.A.). augustin@angiogenese.de.

Abstract

OBJECTIVE:

Vascular smooth muscle cells (VSMC) play a key role in the pathogenesis of atherosclerosis, the globally leading cause of death. The transmembrane orphan receptor endosialin (CD248) has been characterized as an activation marker of cells of the mesenchymal lineage including tumor-associated pericytes, stromal myofibroblasts, and activated VSMC. We, therefore, hypothesized that VSMC-expressed endosialin may display functional involvement in the pathogenesis of atherosclerosis.

APPROACH AND RESULTS:

Expression of endosialin was upregulated during atherosclerosis in apolipoprotein E (ApoE)-null mice and human atherosclerotic samples analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry. Atherosclerosis, assessed by Oil Red O staining of the descending aorta, was significantly reduced in ApoE/endosialin-deficient mice on Western-type diet. Marker analysis of VSMC in lesions induced by shear stress-modifying cast implantation around the right carotid artery identified a more pronounced contractile VSMC phenotype in the absence of endosialin. Moreover, in addition to contributing to neointima formation, endosialin also potentially regulated the proinflammatory phenotype of VSMC as evidenced in surrogate cornea pocket assay experiments in vivo and corresponding flow cytometry and ELISA analyses in vitro.

CONCLUSIONS:

The experiments identify endosialin as a potential regulator of phenotypic remodeling of VSMC contributing to atherosclerosis. The association of endosialin with atherosclerosis and its absent expression in nonatherosclerotic samples warrant further consideration of endosialin as a therapeutic target and biomarker.

KEYWORDS:

atherosclerosis; cell proliferation; cytokines; inflammation; neointima

PMID:
28126825
DOI:
10.1161/ATVBAHA.116.308455
[Indexed for MEDLINE]

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