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Transition of Macrophages to Fibroblast-Like Cells in Healing Myocardial Infarction
Journal of the American College of Cardiology ( IF 21.7 ) Pub Date : 2019-12-01 , DOI: 10.1016/j.jacc.2019.10.036 Nezam Haider 1 , Lisardo Boscá 2 , H Reinier Zandbergen 3 , Jason C Kovacic 4 , Navneet Narula 5 , Silvia González-Ramos 2 , María Fernandez-Velasco 6 , Sudhanshu Agrawal 7 , Marta Paz-García 8 , Sudhir Gupta 7 , Kristine DeLeon-Pennell 9 , Valentin Fuster 10 , Borja Ibañez 11 , Jagat Narula 4
Journal of the American College of Cardiology ( IF 21.7 ) Pub Date : 2019-12-01 , DOI: 10.1016/j.jacc.2019.10.036 Nezam Haider 1 , Lisardo Boscá 2 , H Reinier Zandbergen 3 , Jason C Kovacic 4 , Navneet Narula 5 , Silvia González-Ramos 2 , María Fernandez-Velasco 6 , Sudhanshu Agrawal 7 , Marta Paz-García 8 , Sudhir Gupta 7 , Kristine DeLeon-Pennell 9 , Valentin Fuster 10 , Borja Ibañez 11 , Jagat Narula 4
Affiliation
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BACKGROUND
Macrophages and fibroblasts are 2 major cell types involved in healing after myocardial infarction (MI), contributing to myocardial remodeling and fibrosis. Post-MI fibrosis progression is characterized by a decrease in cardiac macrophage content. OBJECTIVES
This study explores the potential of macrophages to express fibroblast genes and the direct role of these cells in post-MI cardiac fibrosis. METHODS
Prolonged in vitro culture of human macrophages was used to evaluate the capacity to express fibroblast markers. Infiltrating cardiac macrophages was tracked in vivo after experimental MI of LysM(Cre/+);ROSA26(EYFP/+) transgenic mice. The expression of Yellow Fluorescent Protein (YFP) in these animals is restricted to myeloid lineage allowing the identification of macrophage-derived fibroblasts. The expression in YFP-positive cells of fibroblast markers was determined in myocardial tissue sections of hearts from these mice after MI. RESULTS
Expression of the fibroblast markers type I collagen, prolyl-4-hydroxylase, fibroblast specific protein-1, and fibroblast activation protein was evidenced in YFP-positive cells in the heart after MI. The presence of fibroblasts after MI was evaluated in the hearts of animals after depletion of macrophages with clodronate liposomes. This macrophage depletion significantly reduced the number of Mac3+Col1A1+ cells in the heart after MI. CONCLUSIONS
The data provide both in vitro and in vivo evidence for the ability of macrophages to transition and adopt a fibroblast-like phenotype. Therapeutic manipulation of this macrophage-fibroblast transition may hold promise for favorably modulating the fibrotic response after MI and after other cardiovascular pathological processes.
中文翻译：
巨噬细胞转变为成纤维细胞样细胞在治愈心肌梗塞中
背景巨噬细胞和成纤维细胞是参与心肌梗塞（MI）后愈合的两种主要细胞类型，有助于心肌重塑和纤维化。MI 后纤维化进展的特征在于心脏巨噬细胞含量的减少。目的 本研究探讨巨噬细胞表达成纤维细胞基因的潜力以及这些细胞在 MI 后心脏纤维化中的直接作用。方法 人类巨噬细胞的长期体外培养用于评估表达成纤维细胞标志物的能力。在 LysM(Cre/+);ROSA26(EYFP/+) 转基因小鼠的实验性心肌梗死后，体内跟踪浸润的心脏巨噬细胞。黄色荧光蛋白 (YFP) 在这些动物中的表达仅限于髓系谱系，允许鉴定巨噬细胞衍生的成纤维细胞。在心肌梗死后这些小鼠心脏的心肌组织切片中测定了成纤维细胞标记物在 YFP 阳性细胞中的表达。结果 MI 后心脏 YFP 阳性细胞中证实了成纤维细胞标志物 I 型胶原蛋白、脯氨酰 4-羟化酶、成纤维细胞特异性蛋白 1 和成纤维细胞活化蛋白的表达。在用氯膦酸盐脂质体耗尽巨噬细胞后，在动物心脏中评估 MI 后成纤维细胞的存在。这种巨噬细胞耗竭显着减少了心肌梗死后心脏中 Mac3+Col1A1+ 细胞的数量。结论 该数据为巨噬细胞转变和采用成纤维细胞样表型的能力提供了体外和体内证据。
更新日期：2019-12-01
中文翻译：
巨噬细胞转变为成纤维细胞样细胞在治愈心肌梗塞中
背景巨噬细胞和成纤维细胞是参与心肌梗塞（MI）后愈合的两种主要细胞类型，有助于心肌重塑和纤维化。MI 后纤维化进展的特征在于心脏巨噬细胞含量的减少。目的 本研究探讨巨噬细胞表达成纤维细胞基因的潜力以及这些细胞在 MI 后心脏纤维化中的直接作用。方法 人类巨噬细胞的长期体外培养用于评估表达成纤维细胞标志物的能力。在 LysM(Cre/+);ROSA26(EYFP/+) 转基因小鼠的实验性心肌梗死后，体内跟踪浸润的心脏巨噬细胞。黄色荧光蛋白 (YFP) 在这些动物中的表达仅限于髓系谱系，允许鉴定巨噬细胞衍生的成纤维细胞。在心肌梗死后这些小鼠心脏的心肌组织切片中测定了成纤维细胞标记物在 YFP 阳性细胞中的表达。结果 MI 后心脏 YFP 阳性细胞中证实了成纤维细胞标志物 I 型胶原蛋白、脯氨酰 4-羟化酶、成纤维细胞特异性蛋白 1 和成纤维细胞活化蛋白的表达。在用氯膦酸盐脂质体耗尽巨噬细胞后，在动物心脏中评估 MI 后成纤维细胞的存在。这种巨噬细胞耗竭显着减少了心肌梗死后心脏中 Mac3+Col1A1+ 细胞的数量。结论 该数据为巨噬细胞转变和采用成纤维细胞样表型的能力提供了体外和体内证据。
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