Endothelin-1 (ET-1) production is increased in hypertrophied hearts accompanied with fibrosis. ET-1 is a potent mitogen of fibroblasts and ET receptor antagonists are reported to inhibit the proliferation of fibroblasts and cardiac fibrosis. Peroxisome-proliferator-activated receptor α (PPARα), one of the nuclear hormone receptors, suppresses activator protein-1 (AP-1), one of the nuclear transcription factors. Activation of PPARα is reported to inhibit thrombin-induced ET-1 production by repressing the AP-1 signalling pathway in vascular endothelial cells. We investigated effects of the PPARα activator fenofibrate (80mg/kg per day, per os) on mRNA levels of ET-1, collagen type I and type III and histological features of myocardial fibrosis in hypertrophied rat hearts due to pressure-overload by abdominal aortic banding (AB). The treatment with fenofibrate or vehicle was started 7 days before the AB operation. Four days after the AB operation, fenofibrate treatment significantly reduced ET-1 mRNA expression compared with vehicle treatment in AB rat hearts. Collagen type I and type III mRNA expression, and interstitial and perivascular fibrosis were attenuated in the fenofibrate-treated AB rat group. Since the ET-1 gene has AP-1 response elements in the 5´-flanking region, it is suggested that myocardial fibrosis is effectively inhibited by fenofibrate through suppression of AP-1-mediated ET-1 gene augmentation in the pressure-overloaded heart caused by aortic banding in rats.
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September 2002
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Conference Article|
September 01 2002
Stimulation of peroxisome-proliferator-activated receptor α (PPAR α) attenuates cardiac fibrosis and endothelin-1 production in pressure-overloaded rat hearts
Takehiro OGATA;
Takehiro OGATA
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
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Takashi MIYAUCHI;
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
Dr T. Miyauchi (e-mail [email protected]).
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Satoshi SAKAI;
Satoshi SAKAI
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
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Yoko IRUKAYAMA-TOMOBE;
Yoko IRUKAYAMA-TOMOBE
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
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Katsutoshi GOTO;
Katsutoshi GOTO
†Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, 305-8575, Japan
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Iwao YAMAGUCHI
Iwao YAMAGUCHI
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 284S–288S.
Citation
Takehiro OGATA, Takashi MIYAUCHI, Satoshi SAKAI, Yoko IRUKAYAMA-TOMOBE, Katsutoshi GOTO, Iwao YAMAGUCHI; Stimulation of peroxisome-proliferator-activated receptor α (PPAR α) attenuates cardiac fibrosis and endothelin-1 production in pressure-overloaded rat hearts. Clin Sci (Lond) 1 September 2002; 103 (s2002): 284S–288S. doi: https://doi.org/10.1042/CS103S284S
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