Vascular smooth muscle cells (VSMCs) are exposed to hormonal and mechanical stress in vivo. Hormonal factors have been shown to affect hypoxia-inducible factor-1α (HIF-1α). How mechanical stress affects the regulation of HIF-1α in VSMCs has not been reported previously, and therefore we sought to investigate the regulation of HIF-1α by cyclical mechanical stretch in cultured rat VSMCs. Rat VSMCs grown on a flexible membrane base were stretched by vacuum to 20% of the maximum elongation at 60 cycles/min. The levels of HIF-1α protein began to increase as early as 2 h after stretch was applied and reached a maximum of 2.8-fold over the control by 4 h. Real-time PCR showed that the levels of HIF-1α mRNA increased 2.1-fold after cyclical stretch for 4 h. Cyclical mechanical stretch also increased the immunohistochemical labelling of HIF-1α in VSMCs after cyclical stretch for 4 h. The phosphorylation of p42/p44 mitogen-activated protein kinase (MAP kinase) increased after stretch and this was inhibited by the MAP kinase kinase inhibitors PD98059 and U0126. PD98059 and U0126 also blocked HIF-1α gene expression induced by cyclical stretch. In conclusion, cyclical mechanical stretch activates the gene expression of HIF-1α in cultured VSMCs and this mechanical effect is possibly mediated by the p42/p44 MAP kinase kinase pathway.
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October 2003
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Research Article|
October 01 2003
Regulation of hypoxia-inducible factor-1α by cyclical mechanical stretch in rat vascular smooth muscle cells
Hang CHANG;
Hang CHANG
*Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
†Department of Surgery, Taipei Medical University, Taipei, Taiwan
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Kou-Gi SHYU;
‡Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
§Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
Correspondence: Kou-Gi Shyu, Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Rd, Taipei 111, Taiwan (e-mail shyukg@ms12.hinet.net).
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Bao-Wei WANG;
Bao-Wei WANG
‡Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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Peiliang KUAN
Peiliang KUAN
‡Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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Publisher: Portland Press Ltd
Received:
March 10 2003
Revision Received:
May 13 2003
Accepted:
June 02 2003
Accepted Manuscript online:
June 02 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2003 The Biochemical Society
2003
Clin Sci (Lond) (2003) 105 (4): 447–456.
Article history
Received:
March 10 2003
Revision Received:
May 13 2003
Accepted:
June 02 2003
Accepted Manuscript online:
June 02 2003
Citation
Hang CHANG, Kou-Gi SHYU, Bao-Wei WANG, Peiliang KUAN; Regulation of hypoxia-inducible factor-1α by cyclical mechanical stretch in rat vascular smooth muscle cells. Clin Sci (Lond) 1 October 2003; 105 (4): 447–456. doi: https://doi.org/10.1042/CS20030088
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