TY - JOUR
T1 - Sustained expression of MCP-1 by low wall shear stress loading concomitant with turbulent flow on endothelial cells of intracranial aneurysm
AU - Aoki, Tomohiro
AU - Yamamoto, Kimiko
AU - Fukuda, Miyuki
AU - Shimogonya, Yuji
AU - Fukuda, Shunichi
AU - Narumiya, Shuh
N1 - Funding Information:
T. A. and S. N. were supported by the Coordination Fund from Japan Science and Technology Agency and Astellas Pharma Inc. S.N. is a scientific advisor to Astellas Pharma. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#26861145, T.A.) and by Core Research for Evolutional Science and Technology (CREST) on Chronic Inflammation by the Japan Science and Technology Agency (S.N.). We thank M. Kobori, K. Mizutani, and Y. Imai for technical assistance, and T. Arai and A. Washimi for secretarial assistance.
PY - 2016/5/9
Y1 - 2016/5/9
N2 - INTRODUCTION: 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.RESULTS: 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.CONCLUSIONS: 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.
AB - INTRODUCTION: 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.RESULTS: 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.CONCLUSIONS: 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.
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U2 - 10.1186/s40478-016-0318-3
DO - 10.1186/s40478-016-0318-3
M3 - Article
C2 - 27160403
AN - SCOPUS:84991597863
VL - 4
SP - 48
JO - Acta neuropathologica communications
JF - Acta neuropathologica communications
SN - 2051-5960
IS - 1
ER -