Fibroblasts in post-infarction inflammation and cardiac repair.
Fibroblasts in post-infarction inflammation and cardiac repair.
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DOI：
10.1016/j.bbamcr.2012.08.023
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发表时间：
2013-04
影响因子：
5.1
通讯作者：
Frangogiannis, Nikolaos G.
中科院分区：
文献类型：
--
作者：
Chen, Wei;Frangogiannis, Nikolaos G.
成纤维细胞是心脏间质中的主要细胞类型。作为成年哺乳动物心脏中主要的基质生成细胞，成纤维细胞维持细胞外基质网络的完整性，从而保持几何形状和功能。心肌梗塞后，成纤维细胞经历动态表型改变并指导修复反应。由于其战略位置，心脏成纤维细胞充当感知损伤并激活分泌细胞因子和趋化因子的炎性体的前哨细胞。在愈合的增殖阶段，梗死成纤维细胞经历肌成纤维细胞转分化，形成应力纤维并表达收缩蛋白（例如α-平滑肌肌动蛋白）。机械应力、转化生长因子 (TGF)-β/Smad3 信号传导和细胞外基质组成的改变诱导肌成纤维细胞表型的获得。在梗塞的高度细胞化和生长因子丰富的环境中，活化的肌成纤维细胞产生基质蛋白、蛋白酶及其调节基质代谢的抑制剂。随着梗塞的成熟，交联基质和生长因子撤退对肌成纤维细胞的“应激屏蔽”可能会诱导静止并最终导致细胞凋亡。由于成纤维细胞在梗塞后心脏重塑中发挥关键作用，因此成为心肌梗塞后有希望的治疗靶点。然而，成纤维细胞功能的复杂性和临床背景下梗塞后重塑的病理生理异质性阻碍了临床转化中过于简单化的方法。
Fibroblasts are the predominant cell type in the cardiac interstitium. As the main matrix-producing cells in the adult mammalian heart, fibroblasts maintain the integrity of the extracellular matrix network, thus preserving geometry and function. Following myocardial infarction fibroblasts undergo dynamic phenotypic alterations and direct the reparative response. Due to their strategic location, cardiac fibroblasts serve as sentinel cells that sense injury and activate the inflammasome secreting cytokines and chemokines. During the proliferative phase of healing, infarct fibroblasts undergo myofibroblast transdifferentiation forming stress fibers and expressing contractile proteins (such as α-smooth muscle actin). Mechanical stress, Transforming Growth Factor (TGF)-β/Smad3 signaling and alterations in the composition of the extracellular matrix induce acquisition of the myofibroblast phenotype. In the highly cellular and growth factor-rich environment of the infarct, activated myofibroblasts produce matrix proteins, proteases and their inhibitors regulating matrix metabolism. As the infarct matures, “stress-shielding” of myofibroblasts by the cross-linked matrix and growth factor withdrawal may induce quiescence and ultimately cause apoptotic death. Because of their critical role in post-infarction cardiac remodeling, fibroblasts are promising therapeutic targets following myocardial infarction. However, the complexity of fibroblast functions and the pathophysiologic heterogeneity of post-infarction remodeling in the clinical context discourage oversimplified approaches in clinical translation.
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DOI：
10.3109/08977194.2011.595714
发表时间：
2011-10
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Biernacka A;Dobaczewski M;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
3.2
作者：
Bujak, Marcin;Frangogiannis, Nikolaos G.
通讯作者：
Frangogiannis, Nikolaos G.
DOI：
10.1152/ajpheart.00514.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Banerjee, Indroneal;Fuseler, John W.;Baudino, Troy A.
通讯作者：
Baudino, Troy A.
影响因子：
20.1
作者：
Bujak M;Dobaczewski M;Gonzalez-Quesada C;Xia Y;Leucker T;Zymek P;Veeranna V;Tager AM;Luster AD;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
--
作者：
BarcellosHoff, MH;Dix, TA
通讯作者：
Dix, TA