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N-terminal kinase, and c-Src are activated in human aortic smooth muscle cells by pressure stress

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Abstract

Mechanical forces related to pressure and flow are important for cell hypertrophy and proliferation. There are still a few studies that examine responses of human vascular smooth muscle cells to pure pressure stress (transmural pressure). It is unclear as to which mechanisms are involved in cellular responses to pressure elevation. On the other hand, although the involvement of the local renin-angiotensin system (RAS) in pressure-induced responses was reported, the results were contradictory. It still remains to be determined whether RAS in human vascular smooth muscle cells is activated by pure pressure stress. We studied the upstream signal transduction events of extracellular signal kinase (ERK) in response to atmospheric pressure stress and involvement of angiotensin II in pressure-induced cell proliferation in human aortic smooth muscle cells (HASMC). A pressure-loading apparatus was set up to examine the effects of atmospheric pressure on human aortic smooth muscle cells. Pressure application of 160 mmHg for 3 h produced cell proliferation and activated ERK and c-JUN N-terminal kinase (JNK). ACE inhibitor suppressed all of them. ERK kinase (MEK) inhibitor also suppressed cell proliferation stimulated by pure pressure. The phosphorylated c-Src was increased by pure pressure stress. The treatment with c-Src kinase inhibitor suppressed pressure-induced proliferative response. In summary, our study found that ERK activation mediated pure pressure-induced proliferative response of HASMC. This activation was partly mediated by c-Src. (Mol Cell Biochem 262: 71–78, 2004)

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Authors and Affiliations

  1. Department of Pathophysiology and Laboratory Medicine, Hokkaido University Graduate School of Medicine, N-15 W-7, Kita-Ku Sapporo, Japan

    Noriteru Morita, Kenji Iizuka & Takeshi Murakami

  2. Department of Pathophysiology and Laboratory Medicine, Hokkaido University Graduate School of Medicine, N-15 W-7, Kita-Ku Sapporo, Japan

    Hideaki Kawaguchi

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  1. Noriteru Morita
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  2. Kenji Iizuka
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  3. Takeshi Murakami
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  4. Hideaki Kawaguchi
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Morita, N., Iizuka, K., Murakami, T. et al. N-terminal kinase, and c-Src are activated in human aortic smooth muscle cells by pressure stress. Mol Cell Biochem 262, 71–78 (2004). https://doi.org/10.1023/B:MCBI.0000038218.09259.1c

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  • DOI: https://doi.org/10.1023/B:MCBI.0000038218.09259.1c

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