title: Cyclic stretch downregulates arterial vascular connexin43 protein expression: an ex vivo study.
abstract: Vascular cells may communicate through gap junctions that are formed by connexin (Cx) proteins. We investigated differential regulation of arterial gap junctions by steady and cyclic stretch and the underlying mechanotransduction pathways. Ex vivo culture of rabbit thoracic aortas was used to investigate regulation of Cx43 by cyclic stretch. After culturing for 6 or 24 h, Cx43 protein levels were quantified using Western blot. Cultures under a pulsatile pressure (mean 80 mmHg, pulse 30 mmHg) decreased Cx43 protein at both 6 and 24 h as compared with cultures under a steady pressure (80 mmHg). The regulation of Cx43 protein was mediated by pulsatile pressure-induced cyclic stretch, not by cyclic stress. Protein levels of active and total Src were also decreased by cyclic stretch at 24 h. The Src- specific inhibitor PP1 in steady culture only or in both steady and pulsatile culture conditions eliminated the difference in Cx43 protein levels between the two culture conditions. Addition of reactive oxygen species inhibitor apocynin to the pulsatile culture abolished the differences in Src and Cx43 protein levels between the two cultures. Thus, Src and reactive oxygen species appear to play a role in cyclic stretch-mediated regulation of Cx43 protein. These results are likely to have important implications in cardiovascular physiology and pathophysiology under conditions wherein significant alterations in the level of cyclic stretch are present.
authors.affiliation: Cardiovascular Systems Laboratory, Department of Bioengineering, University of Pittsburgh, 306 Center for Bioengineering, 300 Technology Drive, Pittsburgh, PA 15219, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Sanjeev G
authors.initials: SG
authors.lastname: Shroff
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D001783:Blood Flow Velocity / Q000502:physiology; D018031:Connexin 43 / Q000502:physiology*; D015536:Down-Regulation; D055119:Elastic Modulus / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D066298:In Vitro Techniques; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D010507:Periodicity; D011673:Pulsatile Flow / Q000502:physiology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D033081:Shear Strength / Q000502:physiology; D013314:Stress, Mechanical
chemical_list: D018031:Connexin 43; D017382:Reactive Oxygen Species