Antihypertrophic effects of adiponectin on cardiomyocytes are associated with the inhibition of heparin-binding epidermal growth factor signaling

作者：Liao Yulin^*; Xuan Wanling; Zhao Jing; Bin Jianpin; Zhao Hui; Asakura Masanori; Funahashi Tohru; Takashima Seiji; Kitakaze Masafumi

来源：Biochemical and Biophysical Research Communications, 2010, 393(3): 519-525.

DOI：10.1016/j.bbrc.2010.02.039

• Adiponectin
• Heparin-binding epidermal growth factor
• Myocardial hypertrophy
• Mouse

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.

• 单位
  南方医科大学