Monocytic fibroblast precursors mediate fibrosis in angiotensin-II-induced cardiac hypertrophy.
Monocytic fibroblast precursors mediate fibrosis in angiotensin-II-induced cardiac hypertrophy.
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DOI：
10.1016/j.yjmcc.2010.05.005
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发表时间：
2010-09
影响因子：
5
通讯作者：
Entman ML
中科院分区：
文献类型：
--
作者：
Haudek SB;Cheng J;Du J;Wang Y;Hermosillo-Rodriguez J;Trial J;Taffet GE;Entman ML
血管紧张素-II(Ang-II)是心脏肥大和衰竭的病理生理学过程中产生的一种类血管紧张素。除了在心脏和平滑肌收缩和盐滞留方面发挥作用外，它还被证明在心脏间质炎症反应和伴随心力衰竭的纤维化中发挥重要作用。在这项研究中，我们研究了一种血管紧张素-II注射模型，以阐明间质纤维化与组织炎症反应的启动之间的早期细胞机制。持续输注Ang-II导致心脏胶原沉积增加。Ang-II输注后，骨髓来源的CD34+/CD45+成纤维细胞表达I型胶原和心脏成纤维细胞标志物DDR2，而结构成纤维细胞为CD34-/CD45-。单核细胞趋化蛋白(MCP)-1基因缺失(MCP-1-KO小鼠)可阻止Ang-II诱导的心肌纤维化和CD34+/CD45+成纤维细胞的出现。实时定量聚合酶链式反应显示，血管紧张素Ⅱ处理的心脏有显著的I型和III型胶原、转化生长因子-MCP-1和肿瘤坏死因子β基因的表达；而在血管紧张素Ⅱ-1-KO处理的心脏中，这一点是不存在的。在野生型和MCP-1-KO小鼠中，Ang-II输注均导致心肌肥厚、收缩功能增强和高血压，在6周的输注过程中，WT和MCP-1-KO小鼠之间无显著差异。总之，Ang-II诱导的心脏非适应性纤维化的发展需要MCP-1的诱导，MCP-1调节CD34+/CD45+成纤维细胞前体细胞的摄取和分化。与炎症和纤维化反应相反，MCP-1在前6周对Ang-II的血流动力学反应没有影响。
Angiotensin-II (Ang-II) is an autacoid generated as part of the pathophysiology of cardiac hypertrophy and failure. In addition to its role in cardiac and smooth muscle contraction and salt retention, it was shown to play a major role in the cardiac interstitial inflammatory response and fibrosis accompanying cardiac failure. In this study, we examined a model of Ang-II infusion to clarify the early cellular mechanisms linking interstitial fibrosis with the onset of the tissue inflammatory response. Continuous infusion of Ang-II resulted in increased deposition of collagen in the heart. Ang-II infusion also resulted in the appearance of distinctive small, spindle-shaped, bone marrow-derived CD34+/CD45+ fibroblasts that expressed collagen type I and the cardiac fibroblast marker DDR2 while structural fibroblasts were CD34-/CD45-. Genetic deletion of monocyte chemoattractant protein (MCP)-1 (MCP-1-KO mice) prevented the Ang-II-induced cardiac fibrosis and the appearance of CD34+/CD45+ fibroblasts. Real-time PCR in Ang-II-treated hearts revealed a striking induction of types I and III collagen, TGF-β1, and TNF mRNA expression; this was obviated in Ang-II-infused MCP-1-KO hearts. In both wild-type and MCP-1-KO mice, Ang-II infusion resulted in cardiac hypertrophy, increased systolic function and hypertension which were not significantly different between the WT and MCP-1-KO mice over the 6 week course of infusion. In conclusion, the development of Ang-II-induced non-adaptive fibrosis in the heart required induction of MCP-1, which modulated the uptake and differentiation of a CD34+/CD45+ fibroblast precursor population. In contrast to the inflammatory and fibrotic response, the hemodynamic response to Ang-II was not affected by MCP-1 in the first 6 weeks.
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影响因子：
--
作者：
Basso, N;Paglia, N;Inserra, F
通讯作者：
Inserra, F
影响因子：
6
作者：
Lakshminarayanan, V;Lewallen, M;Entman, ML
通讯作者：
Entman, ML
DOI：
10.1152/ajpheart.2001.281.6.h2549
发表时间：
2001-12-01
影响因子：
4.8
作者：
Nossuli, TO;Frangogiannis, NG;Entman, ML
通讯作者：
Entman, ML
影响因子：
10.8
作者：
Haudek, Sandra B.;Gupta, Damon;Entman, Mark L.
通讯作者：
Entman, Mark L.
影响因子：
19.6
作者：
Hilgers, KF;Hartner, A;Mann, JFE
通讯作者：
Mann, JFE