title: Lung ischemia: a model for endothelial mechanotransduction.
abstract: Endothelial cells in vivo are constantly exposed to shear associated with blood flow and altered shear stress elicits cellular responses (mechanotransduction). This review describes the role of shear sensors and signal transducers in these events. The major focus is the response to removal of shear as occurs when blood flow is compromised (i.e., ischemia). Pulmonary ischemia studied with the isolated murine lung or flow adapted pulmonary microvascular endothelial cells in vitro results in endothelial generation of reactive oxygen species (ROS) and NO. The response requires caveolae and is initiated by endothelial cell depolarization via K(ATP) channel closure followed by activation of NADPH oxidase (NOX2) and NO synthase (eNOS), signaling through MAP kinases, and endothelial cell proliferation. These physiological mediators can promote vasodilation and angiogenesis as compensation for decreased tissue perfusion.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania Medical Center, 1 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, 19104-6068, USA.
authors.forename: Shampa
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Chapman
authors.forename: Aron B
authors.initials: AB
authors.lastname: Fisher
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D054086:KATP Channels / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology; D040542:Mechanotransduction, Cellular; D051379:Mice; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D054086:KATP Channels; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002118:Calcium