Valsartan blocks thrombospondin/transforming growth factor/Smads to inhibit aortic remodeling in diabetic rats.
Valsartan blocks thrombospondin/transforming growth factor/Smads to inhibit aortic remodeling in diabetic rats.
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缬沙坦阻断血小板反应蛋白/转化生长因子/Smads 以抑制糖尿病大鼠的主动脉重塑。
DOI：
10.1186/s13000-015-0246-8
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发表时间：
2015-04-02
影响因子：
2.6
通讯作者：
Zhong M
中科院分区：
文献类型：
--
作者：
Sun H;Zhao Y;Bi X;Li S;Su G;Miao Y;Ma X;Zhang Y;Zhang W;Zhong M
血管紧张素II（Ang II）和转化生长因子β（TGFβ）与糖尿病并发症的发病机制密切相关。我们的目的是确定异常的血小板反应蛋白 1 (TSP1) 介导的 TGFβ1/Smads 信号通路是否特异性影响糖尿病大鼠的血管纤维化，以及 Ang II 亚型 1 受体阻滞剂缬沙坦是否具有抗纤维化作用。年龄匹配的雄性 Wistar 大鼠被随机分为 3 组：对照组（n = 8）、糖尿病组（n = 16）和缬沙坦（30 mg/kg/天）（n = 16）。 2型糖尿病（T2DM）是由高热量饮食和链脲佐菌素注射诱发的。通过超声心动图和心导管插入术评估胸主动脉的形态和生物力学特性。 Masson染色用于细胞外基质（ECM）的组织学评估。通过免疫组织化学和实时定量逆转录聚合酶链反应分析 TSP1 介导的 TGFβ1/Smads 信号通路中各成分的表达。与对照组相比，糖尿病主动脉的扩张性和顺应性降低，且 ECM 沉积过多。 TSP1介导的TGFβ1/Smads信号通路中的成分，包括TSP1、TGFβ1、TGFβII型受体(TβRII)、Smad2和Smad3，在糖尿病主动脉血管平滑肌细胞质中积累，其蛋白和mRNA水平上调。所有这些异常现象均被缬沙坦减弱。 TSP1 介导的 TGFβ1/Smads 通路激活在 T2DM 大鼠大血管重塑中发挥重要作用。缬沙坦可以阻断该途径并改善血管纤维化。本文的虚拟幻灯片可以在这里找到：http://www.diagnosticpathology.diagnomx.eu/vs/1053842818141195
Angiotensin II (Ang II) and transforming growth factor β (TGFβ) are closely involved in the pathogenesis of diabetic complications. We aimed to determine whether an aberrant thrombospondin 1 (TSP1)–mediated TGFβ1/Smads signaling pathway specifically affects vascular fibrosis in diabetic rats and whether valsartan, an Ang II subtype 1 receptor blocker, has an anti-fibrotic effect. Age-matched male Wistar rats were randomly divided into 3 groups: control (n = 8), diabetes (n = 16) and valsartan (30 mg/kg/day) (n = 16). Type 2 diabetes mellitus (T2DM) was induced by a high-calorie diet and streptozotocin injection. Morphological and biomechanical properties of the thoracic aorta were assessed by echocardiography and cardiac catheterization. Masson staining was used for histological evaluation of extracellular matrix (ECM). The expression of components in the TSP1–mediated TGFβ1/Smads signaling pathway was analyzed by immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction. As compared with controls, diabetic aortas showed reduced distensibility and compliance, with excess ECM deposition. Components in the TSP1-mediated TGFβ1/Smads signaling pathway, including TSP1, TGFβ1, TGFβ type II receptor (TβRII), Smad2 and Smad3, were accumulated in vascular smooth muscle cytoplasm of diabetic aortas and their protein and mRNA levels were upregulated. All these abnormalities were attenuated by valsartan. TSP1-mediated TGFβ1/Smads pathway activation plays an important role in marcovascular remodeling in T2DM in rat. Valsartan can block the pathway and ameliorate vascular fibrosis. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1053842818141195
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影响因子：
120.7
作者：
Cooper-DeHoff, Rhonda M.;Gong, Yan;Handberg, Eileen M.;Bavry, Anthony A.;Denardo, Scott J.;Bakris, George L.;Pepine, Carl J.
通讯作者：
Pepine, Carl J.
影响因子：
19
作者：
Clarke, David C.;Liu, Xuedong
通讯作者：
Liu, Xuedong
影响因子：
6
作者：
Belmadani, Souad;Bernal, Juan;Berecek, Kathleen H.
通讯作者：
Berecek, Kathleen H.
DOI：
10.1152/ajprenal.00139.2003
发表时间：
2004-02-01
影响因子：
4.2
作者：
Naito, T;Masaki, T;Kohno, N
通讯作者：
Kohno, N
影响因子：
6.1
作者：
Soma, Jun;Sato, Kozo;Tsuchiya, Yoshinori
通讯作者：
Tsuchiya, Yoshinori