title: Midkine exacerbates pressure overload-induced cardiac remodeling.
abstract: Midkine is a multifunctional growth factor, and its serum levels are increased with the functional severity of heart failure. This study aimed to examine the role of midkine in heart failure pathogenesis. Midkine expression levels were increased in the kidney and lung after transverse aortic constriction (TAC) surgery, but not sufficiently increased in the heart. After TAC, phosphorylation of extracellular signal-regulated kinase1/2 and AKT, and the expression levels of foetal genes in the heart were considerably increased in transgenic mice with cardiac-specific overexpression of midkine (MK-Tg) compared with wild-type (WT) mice. MK-Tg mice showed more severe cardiac hypertrophy and dysfunction, and showed lower survival rate after TAC than WT mice. We conclude that midkine plays a critical role in cardiac hypertrophy and remodelling.
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Netsu
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan. Electronic address: tshishid@med.id.yamagata-u.ac.jp.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shishido
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kitahara
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Funayama
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Narumi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Kadowaki
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Arimoto
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiyama
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacology, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Woo
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003250:Constriction; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005355:Fibrosis; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008822:Mice, Transgenic; D000078792:Midkine; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011312:Pressure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D016207:Cytokines; D000078792:Midkine; D051057:Proto-Oncogene Proteins c-akt
keywords: ANP; BNP; CTGF; Cardio–renal interaction; ERK; GAPDH; Heart failure; MHC; Midkine; PI3K; TAC; atrial natriuretic peptide; brain natriuretic peptide; connective tissue growth factor; extracellular signal-regulated kinase; glyceraldehyde 3-phosphate dehydrogenase; myosin heavy chain; phosphatidylinositol 3-kinase; transverse aortic constriction