Departmental sources Background: Cardiac hypertrophy usually results in heart failure and is an important cause of mortality worldwide. Wnt/bcatenin signaling pathway hyper-activation is involved in the pathogenesis and progression of cardiac hypertrophy. Wnt-C59 is a small molecular compound, which strongly and specifically targets at Porcupine to pharmacologically inhibit Wnt palmitoylation, secretion, and other biological activities. However, the role of Wnt-C59 in cardiac hypertrophy remains unknown. Material/Methods: We performed transverse aortic constriction (TAC) in adult male mice to induce pressure overload and establish an in vivo model of cardiac hypertrophy. Angiotensin II (Ang-II) was utilized to culture cardiomyocyte to establish a model of in vitro cardiomyocyte hypertrophy. Daily administration of Porcupine inhibitor Wnt-C59 was performed for 4 weeks after TAC surgery. Results: Wnt-C59 significantly improved cardiac function and enhanced survival of mice subjected to TAC surgery. Histologically, Wnt-C59 attenuated TAC-induced increase in heart mass, cross-section area of cardiomyocyte, cardiac fibrosis, cardiomyocyte apoptosis, and expression of the hypertrophic biomarkers b-MHC, ANP, and BNP. TAC-induced oxidative stress was also ameliorated by Wnt-C59. Wnt-C59 attenuated Ang-II-induced in vitro cardiomyocyte hypertrophy, as indicated by decreased cell size and lower expression of ANP, BNP, and b-MHC. Moreover, Wnt/b-catenin activation was blocked by Wnt-C59 in cardiac hypertrophy, as indicated by decreased protein expression of Wnt3a and b-catenin and the Wnt target genes cyclin D1 and c-Myc. Conclusions: Collectively, Porcupine inhibitor Wnt-C59 attenuates pressure overload-induced cardiac hypertrophic via interruption of the Wnt/b-catenin signaling pathway, and it might be a promising drug for patients with cardiac hypertrophy.
Aliskiren (ALS) is well known for its antihypertensive properties. However, the potential underlying the molecular mechanism and the anti-hypertrophic effect of ALS have not yet been fully elucidated. The aim of the present study was to investigate the role of ALS in mammalian target of rapamycin (mTOR) and apoptosis signaling using in vivo and in vitro models of cardiac hypertrophy. A rat model of cardiac hypertrophy was induced by isoproterenol treatment (5 mg Á kg-1 Á day-1) for 4 weeks, with or without ALS treatment at 20 mg Á kg-1 Á day-1. The expression of hypertrophic, fibrotic, and apoptotic markers was determined by RT-qPCR. The protein expression of apoptotic markers mTOR and p-mTOR was assessed by western blot analysis. The proliferation of H9C2 cells was monitored using the MTS assay. Cell apoptosis was analyzed using flow cytometry. In vivo, isoproterenol-treated rats exhibited worse cardiac function, whereas ALS treatment reversed these dysfunctions, which were associated with changes in p-mTOR, Bcl-2, Bax, and cleaved caspase-3 expression, as well as the number of apoptotic cells. In vitro, H9C2 cardiomyocyte viability was significantly inhibited and cardiac hypertrophy was induced by Ang II administration, but ALS reversed Ang II-induced H9C2 cardiomyocyte hypertrophy and death. Furthermore, Ang II triggered the activation of the mTOR and apoptosis pathways in hypertrophic cardiomyocytes that were inhibited by ALS treatment. These results indicated that ALS alleviated cardiac hypertrophy through inhibition of the mTOR and apoptosis pathways in cardiomyocytes.
An eco-friendly medium-density fiberboard (MDF) was prepared using vanillin (V) crosslinked chitosan (CS) adhesive through a hot-pressing process. The cross-linking mechanism and the effect of different proportions of added chitosan/vanillin on the mechanical properties and dimensional stability of MDF were investigated. The results showed that vanillin and chitosan are crosslinked to form a three-dimensional network structure due to the Schiff base reaction between the aldehyde group of vanillin and the amino group of chitosan. At the same time, when the mass ratio between vanillin/chitosan was 2:1, MDF obtained the best mechanical properties, the maximum modulus of rupture (MOR) of 20.64 MPa, the mean modulus of elasticity (MOE) of 3005 MPa, the mean internal bonding (IB) of 0.86 MPa, and the mean thickness swelling (TS) of 14.7%. Therefore, the MDF bonded with V-crosslinked CS can be a promising candidate for environmentally-friendly wood-based panels.
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