title: Myeloid mineralocorticoid receptor deficiency inhibits aortic constriction-induced cardiac hypertrophy in mice.
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.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yu Yao
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Frieler
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiao Jun
authors.initials: XJ
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wu Chang
authors.initials: WC
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xue Nan
authors.initials: XN
authors.lastname: Sun
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qing Zhen
authors.initials: QZ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Shu Min
authors.initials: SM
authors.lastname: Ma
authors.affiliation: Department of Nephrology, Xuhui Central Hospital, Shanghai, China.
authors.forename: Baozhuan
authors.initials: B
authors.lastname: Huang
authors.affiliation: German Cancer Research Center (DKFZ), Division Molecular Biology of the Cell I, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Berger
authors.affiliation: Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Wang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Division of Cancer Research and Training, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, United States of America; David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Sheng Zhong
authors.initials: SZ
authors.lastname: Duan
authors.affiliation: 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; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Mortensen
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D003251:Constriction, Pathologic / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism
chemical_list: C000598932:Nr3c2 protein, mouse; D017382:Reactive Oxygen Species; D018161:Receptors, Mineralocorticoid