Author:
Methatham Thanachai,Tomida Shota,Kimura Natsuka,Imai Yasushi,Aizawa Kenichi
Abstract
AbstractIn heart failure (HF) caused by hypertension, the myocyte size increases, and the cardiac wall thickens. A low-molecular-weight compound called ICG001 impedes β-catenin-mediated gene transcription, thereby protecting both the heart and kidney. However, the HF-preventive mechanisms of ICG001 remain unclear. Hence, we investigated how ICG001 can prevent cardiac hypertrophy and fibrosis induced by transverse aortic constriction (TAC). Four weeks after TAC, ICG001 attenuated cardiac hypertrophy and fibrosis in the left ventricular wall. The TAC mice treated with ICG001 showed a decrease in the following: mRNA expression of brain natriuretic peptide (Bnp), Klf5, fibronectin, β-MHC, and β-catenin, number of cells expressing the macrophage marker CD68 shown in immunohistochemistry, and macrophage accumulation shown in flow cytometry. Moreover, ICG001 may mediate the substrates in the glycolysis pathway and the distinct alteration of oxidative stress during cardiac hypertrophy and HF. In conclusion, ICG001 is a potential drug that may prevent cardiac hypertrophy and fibrosis by regulating KLF5, immune activation, and the Wnt/β-catenin signaling pathway and inhibiting the inflammatory response involving macrophages.
Funder
Jichi Medical University
Ministry of Education, Culture, Sports, Science and Technology of Japan
Publisher
Springer Science and Business Media LLC
Reference61 articles.
1. Benjamin, E. J. et al. Heart disease and stroke statistics—2017 update. Am. Heart Assoc. Circ. 135, e146–e603 (2017).
2. Shimizu, I. & Minamino, T. Physiological and pathological cardiac hypertrophy. J. Mol. Cell. Cardiol. 97, 245–262 (2016).
3. Creemers, E. E. & Pinto, Y. M. Molecular mechanisms that control interstitial fibrosis in the pressure-overloaded heart. Cardiovasc. Res. 89, 265–272 (2011).
4. Travers, J. G., Kamal, F. A., Robbins, J., Yutzey, K. E. & Blaxall, B. C. Cardiac fibrosis: The fibroblast awakens. Circ. Res. 118, 1021–1040 (2016).
5. Kong, P., Christia, P. & Frangogiannis, N. G. The pathogenesis of cardiac fibrosis. Cell. Mol. Life Sci. 71, 549–574 (2014).
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