Antihypertrophic effects of adiponectin on cardiomyocytes are associated with the inhibition of heparin-binding epidermal growth factor signaling.
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.
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. Liao18@msn.com
Yulin
Y
Liao
Wanling
W
Xuan
Jing
J
Zhao
Jianpin
J
Bin
Hui
H
Zhao
Masanori
M
Asakura
Tohru
T
Funahashi
Seiji
S
Takashima
Masafumi
M
Kitakaze
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D002460:Cell Line; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009929:Organ Size; D051381:Rats; D015398:Signal Transduction
D052242:Adiponectin; C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D020097:Natriuretic Peptide, Brain