Akitsugu Kawashima    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Associate Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Dedifferentiation of smooth muscle cells in intracranial aneurysms and its potential contribution to the pathogenesis.
Journal	Formal name：Scientific reports Abbreviation：Sci Rep ISSN code：20452322/20452322
Domestic / Foregin	Foregin
Volume, Issue, Page	10(1),pp.8330
Author and coauthor	Oka Mieko, Shimo Satoshi, Ohno Nobuhiko, Imai Hirohiko, Abekura Yu, Koseki Hirokazu, Miyata Haruka, Shimizu Kampei, Kushamae Mika, Ono Isao, Nozaki Kazuhiko, Kawashima Akitsugu, Kawamata Takakazu, Aoki Tomohiro
Publication date	2020/05
Summary	Smooth muscle cells (SMCs) are the major type of cells constituting arterial walls and play a role to maintain stiffness via producing extracellular matrix. Here, the loss and degenerative changes of SMCs become the major histopathological features of an intracranial aneurysm (IA), a major cause of subarachnoid hemorrhage. Considering the important role of SMCs and the loss of this type of cells in IA lesions, we in the present study subjected rats to IA models and examined how SMCs behave during disease progression. We found that, at the neck portion of IAs, SMCs accumulated underneath the internal elastic lamina according to disease progression and formed the intimal hyperplasia. As these SMCs were positive for a dedifferentiation marker, myosin heavy chain 10, and contained abundant mitochondria and rough endoplasmic reticulum, SMCs at the intimal hyperplasia were dedifferentiated and activated. Furthermore, dedifferentiated SMCs expressed some pro-inflammatory factors, suggesting the role in the formation of inflammatory microenvironment to promote the disease. Intriguingly, some SMCs at the intimal hyperplasia were positive for CD68 and contained lipid depositions, indicating similarity with atherosclerosis. We next examined a potential factor mediating dedifferentiation and recruitment of SMCs. Platelet derived growth factor (PDGF)-BB was expressed in endothelial cells at the neck portion of lesions where high wall shear stress (WSS) was loaded. PDGF-BB facilitated migration of SMCs across matrigel-coated pores in a transwell system, promoted dedifferentiation of SMCs and induced expression of pro-inflammatory genes in these cells in vitro. Because, in a stenosis model of rats, PDGF-BB expression was expressed in endothelial cells loaded in high WSS regions, and SMCs present nearby were dedifferentiated, hence a correlation existed between high WSS, PDGFB and dedifferentiation in vivo. In conclusion, dedifferentiated SMCs presumably by PDGF-BB produced from hi
DOI	10.1038/s41598-020-65361-x
PMID	32433495