Abstract 19135: Angiotensin II Promotes Aortic Valve Sclerosis Independent of Increased Blood Pressure in Apo-E Deficient Mice
Background: Disease process of aortic valve stenosis has many similarities to that of vascular atherosclerosis. Thus it has been suggested that the activation of renin-angiotensin system is involved in this process, but the direct evidence has been sparse. In this study, we analyzed the aortic valve of apolipoprotein E (apoE)-deficient (−/−) mice infused with angiotensin II (Ang II) and compared it with other vascular lesions like brachiocephalic artery or abdominal aorta.
Methods and Results: Male apo-E−/− mice were fed with normal chow and infused with saline (C, n=8), low-dose AngII (500 ng/kg/min) (L, n=10), or high-dose AngII (1,000 ng/kg/min) (H, n=11) for 28 days. Infusion of Ang II, either L or H, increased systolic blood pressure to a similar extent as compared with S (SBP: 111 ± 2.5 in C vs. 126 ± 2.2 in L, p<0.001; 133 ± 2.5 mmHg in H, p<0.001: L vs. H, p=0.06). The aortic valve thickness increased only in H (22 ± 4.0 in C vs. 35 ± 6.1 in L, p=0.25; C vs. 64 ± 9.8 μm in H, p=0.0003; L vs. H, p=0.005). Next, male apo-E −/− mice (16 week age, infused with 1,000 ng/kg/min of Ang II) were divided into 3 groups: control (C, n=8, with saline), hydralazine (50 mg/kg/day) (Hyd, n=10), and angiotensin receptor blocker olmesartan (5 mg/kg/day) (O, n=15). As shown in Table, olmesartan, but not hydralazine, inhibited valve thickening, disruption of endothelial integrity and expression of myofibroblast. Interestingly, the aortic valve thickness was significantly correlated to abdominal aortic area (R=0.47, P=0.0063), but not to plaque area in brachiocephalic artery (R=0.10, P=0.58).
Conclusion: Ang II is critically involved in development of aortic valve sclerosis independent of increased blood pressure, which is similar to formation of abdominal aortic aneurysm.
- © 2010 by American Heart Association, Inc.