Higher mortality in heterozygous neuropilin-1 mice after cardiac pressure overload.
We previously identified that neuropilin-1 (NP-1) was a co-receptor of vascular endothelial growth factor receptor 2 (VEGFR2) and confirmed that NP-1 knockout mice were embryonic lethal due to impairment of vascular development, while VEGF was reported to be involved in the progression of heart failure. However, it is unknown whether NP-1 has any influence on cardiac function, and it also remains poor understood concerning cardiac expression of NP-1 and its interaction with other VEGF receptors in the heart. Here, we first showed that NP-1 heterozygous mice had significantly higher mortality due to either acute or chronic heart failure in response to left ventricular pressure overload. We also observed that NP-1 mRNA and protein were expressed in both neonatal rat cardiomyocytes and adult murine heart. Furthermore, we found that NP-1 formed complexes with VEGFR1 and VEGFR2, respectively, in cardiomyocytes. These findings suggest that NP-1 should play beneficial role in heart failure.
Li
Fei
F
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Zhao
Hui
H
Liao
Yulin
Y
Takashima
Seiji
S
Asano
Yoshihiro
Y
Shintani
Yasunori
Y
Hori
Masatsugu
M
Kitakaze
Masafumi
M
D000818:Animals; D003250:Constriction; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology*; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D011312:Pressure; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D039942:Neuropilin-1; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2