title: The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice.
abstract: The water channel aquaporin 1 (AQP1) promotes endothelial cell migration. It was hypothesized that AQP1 promotes neovascularization and growth of atherosclerotic plaques.
  
  
  
  AQP1 immunoreactivity and protein abundance was examined in human and murine atherosclerotic lesions and aortic aneurysms. Apolipoprotein E (ApoE) knockout (-/-) and AQP1-/-ApoE-/- mice were developed and fed Western diet (WD) for 8 and 16 weeks to accelerate the atherosclerosis process. In ApoE-/- and AQP1-/-ApoE-/- mice abdominal aortic aneurysms (AAA) were induced by angiotensin II (ANGII) infusion by osmotic minipumps for 4 weeks.
  
  
  
  In human atherosclerotic lesions and AAA, AQP1 immunoreactive protein was associated with intralesional small vessels. In ApoE-/- mouse aorta, APQ1 mRNA levels were increased with time on WD (n = 7-9, P < 0.003). Both in murine lesions at the aortic root and in the abdominal aortic aneurysmal wall, AQP1 immunoreactivity was associated with microvascular structures. The atherosclerotic lesion burden was enhanced significantly in ANGII-infused AQP1-/-ApoE-/- mice compared with ApoE-/- mice, but neither incidence nor progression of AAA was different. The aortic lesion burden increased with time on WD but was not different between ApoE-/- and AQP1-/-ApoE-/- mice at either 8 or 16 weeks (n = 13-15). Baseline blood pressure and ANGII-induced hypertension were not different between genotypes.
  
  
  
  AQP1 is expressed in atherosclerotic lesion neovasculature in human and mouse arteries and AQP1 deficiency augments lesion development in ANGII-promoted atherosclerosis in mice. Normal function of AQP1 affords cardiovascular protection.
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Biology, University of Southern Denmark, Odense C, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Wintmo
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Biology, University of Southern Denmark, Odense C, Denmark.
authors.forename: S H
authors.initials: SH
authors.lastname: Johansen
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Biology, University of Southern Denmark, Odense C, Denmark.
authors.forename: P B L
authors.initials: PBL
authors.lastname: Hansen
authors.affiliation: Department of Cardiothoracic and Vascular Surgery T, University Hospital of Odense, Odense C, Denmark.
authors.forename: J S
authors.initials: JS
authors.lastname: Lindholt
authors.affiliation: Cardiovascular Research Centre, Viborg Hospital, Viborg, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Urbonavicius
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Biology, University of Southern Denmark, Odense C, Denmark.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense C, Denmark.
authors.forename: L M
authors.initials: LM
authors.lastname: Rasmussen
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Biology, University of Southern Denmark, Odense C, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Bie
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Biology, University of Southern Denmark, Odense C, Denmark.
authors.forename: B L
authors.initials: BL
authors.lastname: Jensen
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Biology, University of Southern Denmark, Odense C, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Stubbe
mesh_terms: D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D051398:Aquaporin 1 / Q000096:biosynthesis*; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000633:toxicity
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D051398:Aquaporin 1
keywords: ApoE−/−; aneurysm; aorta; hypertension; lipid; plaque