Efficacy and mechanism of angiotensin II receptor blocker treatment in experimental abdominal aortic aneurysms.
Efficacy and mechanism of angiotensin II receptor blocker treatment in experimental abdominal aortic aneurysms.
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DOI：
10.1371/journal.pone.0049642
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dalman RL
中科院分区：
文献类型：
--
作者：
Iida Y;Xu B;Schultz GM;Chow V;White JJ;Sulaimon S;Hezi-Yamit A;Peterson SR;Dalman RL
尽管肾素-血管紧张素（Ang）系统在腹主动脉瘤（AAA）发病机制中的重要性，但针对该系统预防临床动脉瘤进展的策略仍存在争议且未经证实。我们比较了两种血管紧张素II 1型受体阻滞剂，替米沙坦和厄贝沙坦，在不同的小鼠动脉瘤疾病模型中限制实验性AAA的相对疗效。使用1）雄性ApoE−/−小鼠皮下输注Ang II（1000 ng/kg/min）28天，或2）雄性C57 BL/6小鼠短暂主动脉内输注猪胰弹性蛋白酶诱导AAA。在AAA产生前一周，小鼠开始每天接受厄贝沙坦（50 mg/kg）、替米沙坦（10 mg/kg）、氟伐他汀（40 mg/kg）、波生坦（100 mg/kg）、多西环素（100 mg/kg）或单独的媒介物。通过一系列体内主动脉直径测量、组织病理学和处死时的基因表达分析来确定疗效。在仅喂食标准食物和水的Ang II输注ApoE−/−小鼠（n = 15）中，67%发生了主动脉瘤，40%死于破裂。 值得注意的是，替米沙坦给药小鼠均未发生AAA（n = 14）。 替米沙坦和厄贝沙坦均限制动脉瘤扩大、中膜弹性蛋白溶解、平滑肌衰减、巨噬细胞浸润、外膜新毛细血管形成以及蛋白酶和促炎介质的表达。多西环素、氟伐他汀和波生坦不影响动脉瘤进展。替米沙坦在主动脉内猪胰弹性蛋白酶输注诱导的AAA中也非常有效，这是第二种不需要外源性Ang II输注的AAA模型。替米沙坦以非模型依赖性方式抑制实验性动脉瘤，可能证明在限制临床疾病进展方面有价值。
Despite the importance of the renin-angiotensin (Ang) system in abdominal aortic aneurysm (AAA) pathogenesis, strategies targeting this system to prevent clinical aneurysm progression remain controversial and unproven. We compared the relative efficacy of two Ang II type 1 receptor blockers, telmisartan and irbesartan, in limiting experimental AAAs in distinct mouse models of aneurysm disease. AAAs were induced using either 1) Ang II subcutaneous infusion (1000 ng/kg/min) for 28 days in male ApoE−/− mice, or 2) transient intra-aortic porcine pancreatic elastase infusion in male C57BL/6 mice. One week prior to AAA creation, mice started to daily receive irbesartan (50 mg/kg), telmisartan (10 mg/kg), fluvastatin (40 mg/kg), bosentan (100 mg/kg), doxycycline (100 mg/kg) or vehicle alone. Efficacy was determined via serial in vivo aortic diameter measurements, histopathology and gene expression analysis at sacrifice. Aortic aneurysms developed in 67% of Ang II-infused ApoE−/− mice fed with standard chow and water alone (n = 15), and 40% died of rupture. Strikingly, no telmisartan-treated mouse developed an AAA (n = 14). Both telmisartan and irbesartan limited aneurysm enlargement, medial elastolysis, smooth muscle attenuation, macrophage infiltration, adventitial neocapillary formation, and the expression of proteinases and proinflammatory mediators. Doxycycline, fluvastatin and bosentan did not influence aneurysm progression. Telmisartan was also highly effective in intra-aortic porcine pancreatic elastase infusion-induced AAAs, a second AAA model that did not require exogenous Ang II infusion. Telmisartan suppresses experimental aneurysms in a model-independent manner and may prove valuable in limiting clinical disease progression.
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DOI：
10.1042/cs20090372
发表时间：
2010-03-09
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Daugherty A;Rateri DL;Charo IF;Owens AP;Howatt DA;Cassis LA
通讯作者：
Cassis LA
影响因子：
4.4
作者：
Goergen, Craig J.;Barr, Kyla N.;Huynh, Diem T.;Eastham-Anderson, Jeffrey R.;Choi, Gilwoo;Hedehus, Maj;Dalman, Ronald L.;Connolly, Andrew J.;Taylor, Charles A.;Tsao, Philip S.;Greve, Joan M.
通讯作者：
Greve, Joan M.
影响因子：
15.9
作者：
Bruemmer, D;Collins, AR;Hsueh, WA
通讯作者：
Hsueh, WA
DOI：
10.1111/j.1749-6632.1999.tb07789.x
发表时间：
1999-01-01
期刊：
THE METABOLIC SYNDROME X
影响因子：
--
作者：
Daugherty, A;Cassis, L
通讯作者：
Cassis, L
DOI：
10.1126/science.1192152
发表时间：
2011-04-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Habashi JP;Doyle JJ;Holm TM;Aziz H;Schoenhoff F;Bedja D;Chen Y;Modiri AN;Judge DP;Dietz HC
通讯作者：
Dietz HC