title: Endosialin Promotes Atherosclerosis Through Phenotypic Remodeling of Vascular Smooth Muscle Cells.
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.
  
  
  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.
authors.affiliation: 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.).
authors.forename: Zulfiyya
authors.initials: Z
authors.lastname: Hasanov
authors.affiliation: 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.).
authors.forename: Tina
authors.initials: T
authors.lastname: Ruckdeschel
authors.affiliation: 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.).
authors.forename: Courtney
authors.initials: C
authors.lastname: König
authors.affiliation: 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.).
authors.forename: Carolin
authors.initials: C
authors.lastname: Mogler
authors.affiliation: 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.).
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Kapel
authors.affiliation: 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.).
authors.forename: Claudia
authors.initials: C
authors.lastname: Korn
authors.affiliation: 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.).
authors.forename: Carleen
authors.initials: C
authors.lastname: Spegg
authors.affiliation: 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.).
authors.forename: Viktoria
authors.initials: V
authors.lastname: Eichwald
authors.affiliation: 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.).
authors.forename: Matthias
authors.initials: M
authors.lastname: Wieland
authors.affiliation: 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.).
authors.forename: Sila
authors.initials: S
authors.lastname: Appak
authors.affiliation: 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.
authors.forename: Hellmut G
authors.initials: HG
authors.lastname: Augustin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D058426:Neointima; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D066253:Vascular Remodeling; D014661:Vasoconstriction
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D001057:Apolipoproteins E; C078203:CD248 protein, human; D009363:Neoplasm Proteins; C509258:tumor endothelial marker 1, mouse
keywords: atherosclerosis; cell proliferation; cytokines; inflammation; neointima