title: Sustained expression of MCP-1 by low wall shear stress loading concomitant with turbulent flow on endothelial cells of intracranial aneurysm.
abstract: Enlargement of a pre-existing intracranial aneurysm is a well-established risk factor of rupture. Excessive low wall shear stress concomitant with turbulent flow in the dome of an aneurysm may contribute to progression and rupture. However, how stress conditions regulate enlargement of a pre-existing aneurysm remains to be elucidated.
  
  
  
  Wall shear stress was calculated with 3D-computational fluid dynamics simulation using three cases of unruptured intracranial aneurysm. The resulting value, 0.017 Pa at the dome, was much lower than that in the parent artery. We loaded wall shear stress corresponding to the value and also turbulent flow to the primary culture of endothelial cells. We then obtained gene expression profiles by RNA sequence analysis. RNA sequence analysis detected hundreds of differentially expressed genes among groups. Gene ontology and pathway analysis identified signaling related with cell division/proliferation as overrepresented in the low wall shear stress-loaded group, which was further augmented by the addition of turbulent flow. Moreover, expression of some chemoattractants for inflammatory cells, including MCP-1, was upregulated under low wall shear stress with concomitant turbulent flow. We further examined the temporal sequence of expressions of factors identified in an in vitro study using a rat model. No proliferative cells were detected, but MCP-1 expression was induced and sustained in the endothelial cell layer.
  
  
  
  Low wall shear stress concomitant with turbulent flow contributes to sustained expression of MCP-1 in endothelial cells and presumably plays a role in facilitating macrophage infiltration and exacerbating inflammation, which leads to enlargement or rupture.
authors.affiliation: Center for Innovation in Immunoregulation Technology and Therapeutics, Kyoto University Graduate School of Medicine, Konoe-cho Yoshida, Sakyo-ku, Kyoto, Kyoto, 606-8501, Japan. tomoaoki@kuhp.kyoto-u.ac.jp.|Core Research for Evolutional Science and Technology, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto City, Kyoto, 606-8507, Japan. tomoaoki@kuhp.kyoto-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Aoki
authors.affiliation: System Physiology, Department of Biomedical Engineering, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Core Research for Evolutional Science and Technology, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto City, Kyoto, 606-8507, Japan.|Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto City, Kyoto, 606-8507, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki aza Aoba, Aoba-ku, Sendai City, Miyagi, 980-8578, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimogonya
authors.affiliation: Department of Neurosurgery, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho Fukakusa, Fushimi-ku, Kyoto City, Kyoto, 612-8555, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Center for Innovation in Immunoregulation Technology and Therapeutics, Kyoto University Graduate School of Medicine, Konoe-cho Yoshida, Sakyo-ku, Kyoto, Kyoto, 606-8501, Japan.|Core Research for Evolutional Science and Technology, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto City, Kyoto, 606-8507, Japan.
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002533:Cerebral Angiography; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D018932:Chemokine CCL2 / Q000378:metabolism*; D054428:Chemokine CX3CL1 / Q000378:metabolism; D003198:Computer Simulation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D021621:Imaging, Three-Dimensional; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008955:Models, Cardiovascular; D008959:Models, Neurological; D017207:Rats, Sprague-Dawley; D017423:Sequence Analysis, RNA; D013312:Stress, Physiological / Q000502:physiology*; D014057:Tomography, X-Ray Computed; D059467:Transcriptome
chemical_list: C111835:CCL2 protein, human; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat