Large scale isolation of non-uniform shear stress-responsive genes from cultured human endothelial cells through the preparation of a subtracted cDNA library

Hajime Yoshisue, Keiko Suzuki, Ayako Kawabata, Takeshi Ohya, Hanjun Zhao, Kazuhiro Sakurada, Yoji Taba, Toshiyuki Sasaguri, Naohiko Sakai, Shizuya Yamashita, Yuji Matsuzawa, Hiroshi Nojima

研究成果: Article査読

52 被引用数 (Scopus)

抄録

To investigate the molecular mechanisms responsible for the regional selectivity of early atherogenesis, we have applied a non-uniform shear stress to cultured human umbilical vein endothelial cells (HUVEC). We used a microcarrier culture system and a combination of subtraction and reverse-subtraction methods to isolate a number of genes upregulated by shear stress. The resultant subtracted library includes several known genes (e.g. MCP-1, TM) whose responsiveness to shear stress has been previously reported, indicating that the library is enriched for genes upregulated by shear stress. Also included are atherosclerosis-related genes (e.g. CTGF, IL-8) whose responsiveness to shear stress had not been demonstrated, other known genes whose relationship to atherosclerosis had not been reported, and novel genes. Some responsive to centrifugal force and shear stress (RECS) genes are also upregulated following stimulation by steady laminar shear stress in a parallel plate chamber. Interestingly, the library includes ET-1 and PAI, which are well known atherogenic factors that are downregulated by laminar shear stress. This implies that turbulent shear stress has effects on HUVEC that are different from those elicited by laminar shear stress. Importantly, analysis of specimens taken from human aorta showed that several RECS genes are transcriptionally upregulated in atherosclerotic lesions, suggesting that the subtracted library includes novel therapeutic targets for the treatment of atherosclerosis.

本文言語English
ページ(範囲)323-334
ページ数12
ジャーナルAtherosclerosis
162
2
DOI
出版ステータスPublished - 2002
外部発表はい

ASJC Scopus subject areas

  • 循環器および心血管医学

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