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Myeloid Mineralocorticoid Receptor Deficiency Inhibits Aortic Constriction-Induced Cardiac Hypertrophy in Mice
Authors:Chao Li  Yu Yao Zhang  Ryan A. Frieler  Xiao Jun Zheng  Wu Chang Zhang  Xue Nan Sun  Qing Zhen Yang  Shu Min Ma  Baozhuan Huang  Stefan Berger  Wang Wang  Yong Wu  Ying Yu  Sheng Zhong Duan  Richard M. Mortensen
Abstract: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.
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