on September 4, 2003
Published online before print September 4, 2003, doi: 10.1161/01.ATV.0000093546.10162.B2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 30, 2003
Accepted on August 21, 2003
Hypoxia and Stretch Regulate Intercellular Communication in Vascular Smooth Muscle Cells Through Reactive Oxygen Species Formation
Douglas B. Cowan *;
From the Departments of Anesthesiology, Perioperative and Pain Medicine (D.B.C., M.J., F.X.M.) and Cardiac Surgery (L.M.G., P.J.D.), Children's Hospital Boston and Harvard Medical School, Boston, Mass, and Department of Laboratory Medicine and Pathobiology (S.N.), University of Toronto, Ontario, Canada.
* To whom correspondence should be addressed. E-mail: douglas.cowan{at}tch.harvard.edu.
Objective--We hypothesized that the alterations in vasomotor tone and adaptive remodeling responses that occur in the circulation because of hypoxia were dependent on changes in cell to cell communication through regulation of gap junction protein expression and function. Consequently, we studied the amount, distribution, and permeability of the principal vascular smooth muscle cell (VSMC) gap junction protein, connexin43, in rat aortic cultures exposed to oxygen partial pressures of 150 or 15 mm Hg.
Methods and Results--Immunohistochemical staining, immunoblot assays, and Northern blot analyses demonstrated that connexin43 expression was reversibly increased in hypoxic cultures. As a result, hypoxic cells exhibited greater intercellular communication as determined by fluorescence recovery after photobleaching experiments. Using a fluorogenic substrate, hypoxic VSMCs showed increased reactive oxygen species generation, which could be prevented by the glutathione peroxidase mimic ebselen and the mitochondrial complex I inhibitor rotenone but not with the redox-sensitive thiol pyrrolidine dithiocarbamate. The rise in connexin43 expression attributable to hypoxia could be attenuated by ebselen and rotenone treatment. Interestingly, the previously reported induction of connexin43 expression by tensile stretch was also contingent on oxidative activity.
Conclusions--Hypoxia and stretch increased gap junctional intercellular communication in VSMCs attributable to enhanced connexin43 expression initiated by reactive oxygen species formation.
Key words: gap junction • reactive oxygen species • hypoxia • stretch • smooth muscle cell
This article has been cited by other articles:
 |
|
 |
|
  S. E. Bearden, E. Linn, B. S. Ashley, and R. C. Looft-Wilson Age-related changes in conducted vasodilation: effects of exercise training and role in functional hyperemia Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1717 - R1721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Ali, P. T. Mungai, and P. T. Schumacker Stretch-induced phosphorylation of focal adhesion kinase in endothelial cells: role of mitochondrial oxidants Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L38 - L45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schmelter, B. Ateghang, S. Helmig, M. Wartenberg, and H. Sauer Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain-induced cardiovascular differentiation FASEB J, June 1, 2006; 20(8): 1182 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Li, S.-L. Tzeng, Y.-W. Cheng, and J.-J. Kang Chloramphenicol-induced Mitochondrial Stress Increases p21 Expression and Prevents Cell Apoptosis through a p21-dependent Pathway J. Biol. Chem., July 15, 2005; 280(28): 26193 - 26199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Waypa and P. T. Schumacker Hypoxic pulmonary vasoconstriction: redox events in oxygen sensing J Appl Physiol, January 1, 2005; 98(1): 404 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. N. Tulenko Regulating Cross-Talk Between Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1707 - 1709. [Full Text] [PDF]
|
|