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.
Skip Nav Destination
Article navigation
October 2003
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
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
Search for other works by this author on:
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 [email protected]).
Search for other works by this author on:
Bao-Wei WANG;
Bao-Wei WANG
‡Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
Search for other works by this author on:
Peiliang KUAN
Peiliang KUAN
‡Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
Search for other works by this author on:
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
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |