Angiotensin-converting enzyme-induced activation of local angiotensin signaling is required for ascending aortic aneurysms in fibulin-4-deficient mice.
Angiotensin-converting enzyme-induced activation of local angiotensin signaling is required for ascending aortic aneurysms in fibulin-4-deficient mice.
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血管紧张素转换酶诱导的局部血管紧张素信号的激活是fibulin-4缺陷小鼠中主动脉瘤的升高。
DOI：
10.1126/scitranslmed.3005025
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发表时间：
2013-05-01
影响因子：
17.1
通讯作者：
Yanagisawa H
中科院分区：
文献类型：
--
作者：
Huang J;Yamashiro Y;Papke CL;Ikeda Y;Lin Y;Patel M;Inagami T;Le VP;Wagenseil JE;Yanagisawa H
Aortic aneurysms are life-threatening and often associated with defects in connective tissues and mutations in smooth muscle cell (SMC) contractile proteins. Despite recent advances in understanding altered signaling in aneurysms of Marfan syndrome, the underlying mechanisms and options for pharmacological treatment for other forms of aneurysms are still under investigation. We previously showed in mice that deficiency in the fibulin-4 gene in vascular SMCs (Fbln4SMKO) leads to loss of the SMC contractile phenotype, hyperproliferation and ascending aortic aneurysms. Here, we report that abnormal upregulation of angiotensin converting enzyme (ACE) in SMCs and subsequent activation of angiotensin II (AngII) signaling is involved in the onset of aortic aneurysms in Fbln4SMKO mice. In this model, aneurysm formation was completely prevented by inhibition of the AngII pathway with losartan or captopril within a narrow therapeutic window during the first month of life, even though the altered mechanical properties of blood vessel walls were not reversed by the pharmacological treatment. The therapeutic effects of losartan in Fbln4SMKO mice do not require the AngII receptor type 2 (Agtr2) but likely require both type 1a (Agtr1a) and 1b (Agtr1b) receptors. The results indicate that fibulin-4 is a vascular matrix component required for regulation of local angiotensin signaling, aortic aneurysms, and development and maintenance of the SMC phenotype.
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影响因子：
2
作者：
Dasouki, Majed;Markova, Dessislava;Chu, Mon-Li
通讯作者：
Chu, Mon-Li
DOI：
10.1073/pnas.0908268106
发表时间：
2009-11-10
影响因子：
11.1
作者：
Horiguchi, Masahito;Inoue, Tadashi;Nakamura, Tomoyuki
通讯作者：
Nakamura, Tomoyuki
DOI：
10.1126/science.1192149
发表时间：
2011-04-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Holm TM;Habashi JP;Doyle JJ;Bedja D;Chen Y;van Erp C;Lindsay ME;Kim D;Schoenhoff F;Cohn RD;Loeys BL;Thomas CJ;Patnaik S;Marugan JJ;Judge DP;Dietz HC
通讯作者：
Dietz HC
影响因子：
64.8
作者：
ICHIKI, T;LABOSKY, PA;INAGAMI, T
通讯作者：
INAGAMI, T
DOI：
10.1152/ajpheart.00119.2011
发表时间：
2011-07-01
影响因子：
4.8
作者：
Le, Victoria P.;Knutsen, Russell H.;Wagenseil, Jessica E.
通讯作者：
Wagenseil, Jessica E.