title: Smooth muscle specific overexpression of p22phox potentiates carotid artery wall thickening in response to injury.
abstract: We hypothesized that transgenic mice overexpressing the p22(phox) subunit of the NADPH oxidase selectively in smooth muscle (Tg(p22smc)) would exhibit an exacerbated response to transluminal carotid injury compared to wild-type mice. To examine the role of reactive oxygen species (ROS) as a mediator of vascular injury, the injury response was quantified by measuring wall thickness (WT) and cross-sectional wall area (CSWA) of the injured and noninjured arteries in both Tg(p22smc) and wild-type animals at days 3, 7, and 14 after injury. Akt, p38 MAPK, and Src activation were evaluated at the same time points using Western blotting. WT and CSWA following injury were significantly greater in Tg(p22smc) mice at both 7 and 14 days after injury while noninjured contralateral carotids were similar between groups. Apocynin treatment attenuated the injury response in both groups and rendered the response similar between Tg(p22smc) mice and wild-type mice. Following injury, carotid arteries from Tg(p22smc) mice demonstrated elevated activation of Akt at day 3, while p38 MAPK and Src activation was elevated at day 7 compared to wild-type mice. Both increased activation and temporal regulation of these signaling pathways may contribute to enhanced vascular growth in response to injury in this transgenic model of elevated vascular ROS.
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Manogue
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Bennett
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Drury S
authors.initials: DS
authors.lastname: Holland
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Chung-Sik
authors.initials: CS
authors.lastname: Choi
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Drake
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Taylor
authors.affiliation: Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Weber
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D003573:Cytochrome b Group; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C515614:Cyba protein, mouse; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases