The Water Channel Aquaporin 1 is Associated with Human Atherosclerotic Lesions and Attenuates Progression of Atherosclerosis in Male Mice Independent of Blood Pressure

Abstract

The water channel aquaporin 1 (AQP1) supports tumor growth by facilitating endothelial cell migration in tumor neovascularization. We tested the hypothesis that AQP1 promotes neovascularization of growing vascular lesions and aneurysms using human vascular tissue and AQP1‐/‐Apolipoprotein E (ApoE)‐/‐mice. AQP1 was localized in the neovasculature in human atherosclerotic lesions and in human abdominal aortic aneurysm wall, while in internal thoracic arteries AQP1 was restricted to endothelial cells and adventitial vasa vasorum. In female ApoE‐/‐ mice with lesion burden aortic AQP1 mRNA expression was augmented. AQP1 was localized in endothelial cells, vasa vasorum and intralesional cells at the aortic root. Lesion burden did not differ between AQP1‐/‐ApoE ‐/‐ and ApoE ‐/‐ mice after 8 and 16 weeks on western diet (WD, n =13‐15). Male AQP1‐/‐ApoE‐/‐ mice fed WD and treated with angiotensin II (ANGII) for 4 weeks had elevated atherosclerotic lesion burden compared to ApoE‐/‐ mice (11± 1 vs. 4 ± 2 %, n =10‐11, p<0.02). Freely moving AQP1‐/‐ApoE‐/‐ and ApoE‐/‐ mice showed similar blood pressure responses to ANGII i.v. infusion (60ng/kg*day for 7 d) measured by indwelling catheters (nighttime: 129 ± 4 and 128 ± 5 mmHg, respectively). It is concluded that AQP1 is associated with intralesional neovasculature in humans and mice. AQP1 accelerates ANGII‐induced atherosclerosis in male mice independent of blood pressure.Supported by A. Andersen grant and J. & O. Madsens grant