Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.
Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.
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DOI：
10.1371/journal.pone.0053133
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kubota I
中科院分区：
文献类型：
--
作者：
Suzuki S;Shishido T;Funayama A;Netsu S;Ishino M;Kitahara T;Sasaki T;Katoh S;Otaki Y;Watanabe T;Shibata Y;Mantovani A;Takeishi Y;Kubota I
左心室肥大通过炎症状态和各种细胞因子的刺激而增强。正五聚蛋白3（PTX 3）响应于炎症信号而快速产生，并且在心力衰竭患者中观察到高血浆PTX 3水平。本研究旨在研究PTX 3对压力超负荷引起的心脏肥大和左心室功能不全的影响。对PTX 3系统性敲除（PTX 3-KO）小鼠、心脏特异性过表达PTX 3的转基因小鼠（PTX 3-TG）和相应的野生型（WT）同窝小鼠进行横向主动脉缩窄（TAC）或假手术。在WT小鼠中，TAC后心脏PTX 3表达增加。在体外，过氧化氢诱导心肌细胞和心脏成纤维细胞中的PTX 3的表达。心脏成纤维细胞中重组PTX 3磷酸化细胞外信号调节激酶1/2（ERK 1/2）。与WT小鼠相比，TAC后心脏ERK 1/2和核因子κ B的磷酸化在PTX 3-KO小鼠中减弱，但在PTX 3-TG小鼠中增强。白细胞介素-6和结缔组织生长因子的产生在PTX3-KO小鼠中低于WT小鼠，但在PTX3-TG小鼠中比在WT小鼠中增加。超声心动图显示，在PTX 3-TG小鼠中，左心室功能障碍的不良重构以及间质纤维化增加，而这些反应在PTX 3-KO小鼠中受到抑制。局部炎症介质PTX 3直接调节后负荷增加后的肥厚反应和心室功能障碍。
Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3) is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload. PTX3 systemic knockout (PTX3-KO) mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG), and the respective wild-type (WT) littermate mice were subjected to transverse aortic constriction (TAC) or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal–regulated kinase 1/2 (ERK1/2) in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice. The local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload.
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影响因子：
37.8
作者：
Peri, G;Introna, M;Latini, R
通讯作者：
Latini, R
影响因子：
6
作者：
Kitahara, Tatsuro;Shishido, Tetsuro;Kubota, Isa
通讯作者：
Kubota, Isa
影响因子：
120.7
作者：
Levy, D;Larson, MG;Ho, KKL
通讯作者：
Ho, KKL
影响因子：
37.8
作者：
Nozaki, N;Shishido, T;Kubota, I
通讯作者：
Kubota, I
DOI：
10.1152/ajpheart.00816.2006
发表时间：
2007-05-01
影响因子：
4.8
作者：
Barrick, Cordelia J.;Rojas, Mauricio;Threadgill, David W.
通讯作者：
Threadgill, David W.