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.
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
Abdominal aortic aneurysm (AAA) is an asymptomatic chronic dilatation of the abdominal aorta observed predominantly in elderly males. The disease is usually first discovered at the time of rupture and often has a lethal outcome. The mechanism of aneurysm progression is not well characterized, but includes extensive vascular remodeling. Aquaporin 1 (AQP1) is necessary for endothelial‐ and vascular smooth muscle cell migration in tumors and in hypoxic conditions. Thus, we hypothesized that deletion of AQP1 attenuates the formation and progression of abdominal aortic aneurysms. 10–12 weeks old male ApoE KO and AQP1‐ApoE dKO mice were fed western diet and given angiotensin II (Ang II, 1 μg/kg/min) via subcutaneous osmotic mini pumps for 28 days in order to increase blood pressure and induce AAA formation. At 28 days mice were euthanized and aorta dissected. As expected plasma Ang II concentration did not differ between ApoE KO and AQP1‐ApoE dKO mice (403 ± 96 pg/ml vs. 370 ± 74 pg/ml, n=10–11, p=0.8). There was no difference in the incidence of AAA formation (64% vs. 61%). AAA sizes were similar in ApoE KO and AQP1‐ApoE dKO mice, as measured by outer abdominal diameter (1.45 ± 0.18 mm vs. 1.25 ± 0.18 mm, n = 10–11, p=0.4), and by wet weight of the abdominal aorta (15.4 ± 3.7 mg vs. 14.7 ± 4.3 mg, n= 10–11, p=0.9). It is concluded that in ApoE KO mice on western diet, AQP1 does not contribute significantly to incidence and progression of abdominal aorta aneurysm.Supported by Alfred Andersen grant and Director Jacob Madsen & Olga Madsen's grant
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