title: Increased Age-Related Cardiac Dysfunction in Bradykinin B2 Receptor-Deficient Mice.
abstract: Experimental evidence indicates that the kinin peptide binds to bradykinin B2 receptor (B2R) to trigger various beneficial effects on the cardiovascular system. However, the effects and underlying mechanisms of B2R in cardiac aging remain unknown. A significant age-dependent decrease in B2R expression in the myocardium was observed in C57BL/6J mice. Echocardiographic measurements showed that aging caused a significant cardiac dysfunction in C57BL/6J mice, and importantly B2R deficiency augmented this dysfunction in aging mice. The deficiency of B2R expression in the aging heart repressed p53-pGC-1α-induced mitochondria renewal, increased reactive oxygen species production, and destroyed mitochondrial ultrastructure. Age-related decrease or lack of B2R increased oxidative stress, macrophage infiltration, and inflammatory cytokine expression and compromised antioxidant enzyme expression. Moreover, the inflammatory signals were mainly mediated by the activation of p38 MAPK, JNK, and subsequent translocation of nuclear factor-kappa B to the nucleus. In summary, our data provide evidence that B2R deficiency contributes to the aging-induced cardiac dysfunction, which is likely mediated by increased mitochondrial dysfunction, oxidative stress, and inflammation. This study indicates that preventing the loss of cardioprotective B2R expression may be a novel approach for the prevention and treatment of age-related cardiac dysfunction.
authors.affiliation: Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Department of Geriatric Internal Medicine, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Feng
authors.affiliation: The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Xizhen
authors.initials: X
authors.lastname: Xu
authors.affiliation: The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Ruolan
authors.initials: R
authors.lastname: Dong
authors.affiliation: The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Ben
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Long
authors.affiliation: The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. proftu@tom.com dwwang@tjh.tjmu.edu.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Tu
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D016207:Cytokines / Q000097:blood; D004452:Echocardiography; D005355:Fibrosis / Q000000981:diagnostic imaging / Q000503:physiopathology; D006331:Heart Diseases / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000648:ultrastructure; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000172:deficiency*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D008055:Lipids; D017382:Reactive Oxygen Species; D043782:Receptor, Bradykinin B2
keywords: Aging; Bradykinin B2 receptor; Cardiac dysfunction; Inflammation; Oxidative stress