Kolling Institute for Medical Research, University of Sydney, St Leonards 2065, Australia.
Int J Mol Sci. 2018 Jan 12;19(1):231. doi: 10.3390/ijms19010231.
Historically, increased numbers of mast cells have been associated with fibrosis in numerous cardiac pathologies, implicating mast cells in the development of cardiac fibrosis. Subsequently, several approaches have been utilised to demonstrate a causal role for mast cells in animal models of cardiac fibrosis including mast cell stabilising compounds, rodents deficient in mast cells, and inhibition of the actions of mast cell-specific proteases such as chymase and tryptase. Whilst most evidence supports a pro-fibrotic role for mast cells, there is evidence that in some settings these cells can oppose fibrosis. A major gap in our current understanding of cardiac mast cell function is identification of the stimuli that activate these cells causing them to promote a pro-fibrotic environment. This review will present the evidence linking mast cells to cardiac fibrosis, as well as discuss the major questions that remain in understanding how mast cells contribute to cardiac fibrosis.
从历史上看,大量的肥大细胞与许多心脏病理学中的纤维化有关,这表明肥大细胞参与了心脏纤维化的发展。随后,人们采用了几种方法来在心脏纤维化的动物模型中证明肥大细胞的因果作用,包括肥大细胞稳定化合物、缺乏肥大细胞的啮齿动物,以及抑制肥大细胞特异性蛋白酶(如糜蛋白酶和胰蛋白酶)的作用。尽管大多数证据支持肥大细胞的促纤维化作用,但也有证据表明,在某些情况下,这些细胞可以对抗纤维化。我们目前对心脏肥大细胞功能的理解主要存在一个空白,即确定激活这些细胞的刺激因素,使它们促进促纤维化环境。这篇综述将介绍将肥大细胞与心脏纤维化联系起来的证据,并讨论在理解肥大细胞如何促进心脏纤维化方面仍存在的主要问题。