HOME   Japanese    

Kumamoto University Repository System >
Medicine >
Journal Article (Medicine) >


Files in This Item:

File Description SizeFormat
Hypertension+Res.35.2.194-200.pdf120KbAdobe PDFView/Open
Hypertension+Res.Table+Figure.pdf345KbAdobe PDFView/Open
Title :Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: The critical role of ASK1 and VEGF
Authors :Nako, Hisato
Kataoka, Keiichiro
Koibuchi, Nobutaka
Dong, Yi-Fei
Toyama, Kensuke
Yamamoto, Eiichiro
Yasuda, Osamu
Ichijo, Hidenori
Ogawa, Hisao
Kim-Mitsuyama, Shokei
Issue Date :Feb-2012
Citation jtitle :Hypertension Research
vol. :35
no. :2
start page :194
end page :200
Abstract :This study was undertaken to elucidate a novel mechanism underlying angiotensin II-induced cardiac injury, focusing on the role of oxidative stress and myocardial capillary density. Salt-loaded Dahl salt-sensitive hypertensive rats (DS rats), a useful model for hypertensive cardiac remodeling or heart failure, were orally given irbesartan (an AT1 receptor blocker), tempol (a superoxide dismutase mimetic) or hydralazine (a vasodilator). Irbesartan significantly ameliorated left ventricular ischemia and prevented the development of cardiac hypertrophy and fibrosis in DS rats. The benefits were associated with the attenuation of oxidative stress, normalization of myocardial capillary density and inhibition of capillary endothelial apoptosis. Moreover, DS rats with significant cardiac hypertrophy and fibrosis displayed decreased myocardial vascular endothelial growth factor (VEGF) expression and increased cardiac apoptosis signal-regulating kinase 1 (ASK1) activation. Treatment with irbesartan significantly reversed these phenotypes. Tempol treatment of DS rats mimicked all the above-mentioned effects of irbesartan, indicating the critical role of oxidative stress in cardiac injury. We also investigated the role of VEGF and ASK1 in oxidative stress-induced endothelial apoptosis by using cultured endothelial cells from wild-type and ASK1-deficient mice. Oxidative stress-induced ASK1 activation led to endothelial apoptosis, and VEGF treatment prevented oxidative stress-induced endothelial apoptosis by inhibiting ASK1 activation. We obtained the first evidence that oxidative stress-induced cardiac VEGF repression and ASK1 activation caused the enhancement of endothelial apoptosis and contributed to a decrease in myocardial capillary density. These effects resulted in angiotensin II-induced progression of cardiac injury.
URL :http://www.nature.com/hr/journal/v35/n2/abs/hr2011175a.html
Type Local :雑誌掲載論文
ISSN :09169636
Publisher :Nature Publishing Group
URI :http://hdl.handle.net/2298/25964
Appears in Collections:Journal Article (Medicine)
Please use this identifier to cite or link to this item: http://hdl.handle.net/2298/25964