Abstract | UNLABELLED: MATERIALS AND METHODS: Expression of chymase was evaluated in the hearts of streptozotocin (STZ)-induced diabetic hamsters. The impact of chymase-specific inhibitors, TEI-E00548 and TEI-F00806, on myocardial fibrosis, and increased levels of intracardiac AngII, accumulation of 8-hydroxy-2'-deoxyguanosine (an oxidative stress marker in urine and heart tissue) and expression of heart NOX4 in diabetic hamsters were investigated. RESULTS: Myocardial chymase expression was markedly upregulated in STZ hamsters in a glucose-dependent manner. A total of 8 weeks after STZ administration, the diabetic hamsters showed enhanced oxidative stress and NOX4 expression in the heart, in parallel with increased myocardial AngII production. Oral administration of chymase-specific inhibitors, TEI-F00806 and TEI-E00548, normalized heart AngII levels, and completely reversed NOX4-induced oxidative stress and myocardial fibrosis in STZ-induced diabetic hamsters, although they did not affect the activity of the systemic renin-angiotensin system or systolic blood pressure. CONCLUSIONS: Chymase inhibition might prevent oxidative stress and diabetic cardiomyopathy at an early stage by reducing local AngII production. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00202.x, 2012).
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Authors | Yasutaka Maeda, Toyoshi Inoguchi, Ryoko Takei, Hari Hendarto, Makoto Ide, Tomoaki Inoue, Kunihisa Kobayashi, Hidenori Urata, Akira Nishiyama, Ryoichi Takayanagi |
Journal | Journal of diabetes investigation
(J Diabetes Investig)
Vol. 3
Issue 4
Pg. 354-61
(Aug 20 2012)
ISSN: 2040-1116 [Print] Japan |
PMID | 24843590
(Publication Type: Journal Article)
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