Li Chao, Zhang Yu Yao, Frieler Ryan A, Zheng Xiao Jun, Zhang Wu Chang, Sun Xue Nan, Yang Qing Zhen, Ma Shu Min, Huang Baozhuan, Berger Stefan, Wang Wang, Wu Yong, Yu Ying, Duan Sheng Zhong, Mortensen Richard M
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
PLoS One. 2014 Oct 29;9(10):e110950. doi: 10.1371/journal.pone.0110950. eCollection 2014.
Mineralocorticoid receptor (MR) blockade has been shown to suppress cardiac hypertrophy and remodeling in animal models of pressure overload (POL). This study aims to determine whether MR deficiency in myeloid cells modulates aortic constriction-induced cardiovascular injuries. Myeloid MR knockout (MMRKO) mice and littermate control mice were subjected to abdominal aortic constriction (AAC) or sham operation. We found that AAC-induced cardiac hypertrophy and fibrosis were significantly attenuated in MMRKO mice. Expression of genes important in generating reactive oxygen species was decreased in MMRKO mice, while that of manganese superoxide dismutase increased. Furthermore, expression of genes important in cardiac metabolism was increased in MMRKO hearts. Macrophage infiltration in the heart was inhibited and expression of inflammatory genes was decreased in MMRKO mice. In addition, aortic fibrosis and inflammation were attenuated in MMRKO mice. Taken together, our data indicated that MR deficiency in myeloid cells effectively attenuated aortic constriction-induced cardiac hypertrophy and fibrosis, as well as aortic fibrosis and inflammation.
盐皮质激素受体（MR）阻断已被证明可抑制压力超负荷（POL）动物模型中的心脏肥大和重塑。本研究旨在确定髓系细胞中的MR缺陷是否会调节主动脉缩窄诱导的心血管损伤。将髓系MR基因敲除（MMRKO）小鼠和同窝对照小鼠进行腹主动脉缩窄（AAC）或假手术。我们发现，AAC诱导的心脏肥大和纤维化在MMRKO小鼠中显著减轻。MMRKO小鼠中产生活性氧的重要基因的表达降低，而锰超氧化物歧化酶的表达增加。此外，MMRKO心脏中与心脏代谢重要相关的基因表达增加。MMRKO小鼠心脏中的巨噬细胞浸润受到抑制，炎症基因的表达降低。此外，MMRKO小鼠的主动脉纤维化和炎症也有所减轻。综上所述，我们的数据表明，髓系细胞中的MR缺陷有效地减轻了主动脉缩窄诱导的心脏肥大和纤维化，以及主动脉纤维化和炎症。
