title: Differential responses of pulmonary endothelial phenotypes to cyclical stretch.
abstract: Endothelial phenotypes derived from different pulmonary vascular segments have markedly different permeability response to inflammatory agonists, but their responses to mechanical strain have not been characterized. Therefore, we evaluated the effect of cyclical stretch on cell shape, cell membrane wounding, and junctional beta-catenin in rat pulmonary artery (RPAEC) and microvascular (RPMVEC) endothelial cell monolayers. After 24 h of 24% uniaxial strain at 40 cycles/min, RPAEC but not RPMVEC reoriented transverse to the axis of strain. Total beta-catenin increased in RPAEC but decreased in RPMVEC. Transient plasma membrane wounding was produced by cyclical biaxial strain of 34% or by scratching of monolayers with a needle and was indicated by retention of lysine fixable fluorescent 70 kDa dextran. Junctional beta-catenin was quantified by fluorescence intensity and image analysis. beta-catenin fluorescence was significantly lower in wounded cells than in adjacent uninjured cells in both phenotypes, and the decrease was significantly greater in RPAEC compared to RPMVEC in both scratched (57% vs. 30%) and stretched (55% vs. 37%) cells. Using immunoprecipitation, VE-cadherin-associated beta-catenin decreased significantly in RPAEC (61%) but E-cadherin-associated beta-catenin was not significantly decreased in RPMVEC after 34% biaxial cyclical strain. These data suggest that RPAEC more readily remodel cell-cell adhesions during cyclical stretch than RPMVEC and that a reduced intercellular adhesion adjacent to wounded cells could serve as transvascular leak sites in both phenotypes.
authors.affiliation: Department of Physiology, MSB 3074, University of South Alabama, Mobile, 36688, USA.
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: Adkison
authors.forename: Greg T
authors.initials: GT
authors.lastname: Miller
authors.forename: David S
authors.initials: DS
authors.lastname: Weber
authors.forename: Takashige
authors.initials: T
authors.lastname: Miyahara
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Ballard
authors.forename: J Richard
authors.initials: JR
authors.lastname: Frost
authors.forename: James C
authors.initials: JC
authors.lastname: Parker
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability; D048430:Cell Shape; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D008168:Lung / Q000098:blood supply*; D008833:Microcirculation / Q000166:cytology / Q000293:injuries / Q000502:physiology; D011651:Pulmonary Artery / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D051381:Rats; D013314:Stress, Mechanical; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051176:beta Catenin