Antihypertrophic effects of adiponectin on cardiomyocytes are associated with the inhibition of heparin-binding epidermal growth factor signaling |
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Authors: | Yulin Liao Wanling Xuan Jing Zhao Hui Zhao Tohru Funahashi Masafumi Kitakaze |
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Institution: | a Department of Pathophysiology, China-Japan Collaborative Lab of Cardiovascular Physiology and Key Lab of Shock and Microcirculation Research, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, China b Department of Cardiology in Nanfang Hospital, Southern Medical University, Guangzhou, China c Cardiovascular Division of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan d Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan e Molecular Cardiolvascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan |
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Abstract: | This study was aimed to investigate whether the antihypertrophic effects of adiponectin in murine hearts are associated with the modulation of HB-EGF signaling. We determined the myocardial expressions of adiponectin and adiponectin receptors, brain natriuretic peptide (BNP), and HB-EGF in normal and hypertrophied hearts of adiponectin knockout mice or wild-type mice with transverse aortic constriction (TAC). Then, we observed the effects of adiponectin on cardiac hypertrophy and HB-EGF signaling in cultured neonatal rat cardiomyocytes and whole hearts of adiponectin-null mice. The myocardial mRNA and protein expressions of adiponectin in the hypertrophied hearts were significantly downregulated, and the mRNA expression of adiponectin was inversely correlated with the heart-to-body weight ratio, BNP, and HB-EGF. The TAC-induced cardiac hypertrophy and EGF receptor (EGFR) activation in the adiponectin knockout mice were significantly greater than those in the wild-type mice. Furthermore, in vitro experiments revealed that adiponectin inhibited HB-EGF-stimulated protein synthesis, HB-EGF shedding, and EGFR phosphorylation. We conclude that the inhibition of HB-EGF mediated EGFR activation is one of the alternative mechanisms for the antihypertrophic action of adiponectin. |
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Keywords: | Adiponectin Heparin-binding epidermal growth factor Myocardial hypertrophy Mouse |
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