Angiotensin II (Ang II) is known to elicit cardiac fibrosis by activating the AT1 receptor and CD44 expression in the in vivo model. However, the cellular/molecular mechanisms underlying cardiac fibrosis are still not...Angiotensin II (Ang II) is known to elicit cardiac fibrosis by activating the AT1 receptor and CD44 expression in the in vivo model. However, the cellular/molecular mechanisms underlying cardiac fibrosis are still not well understood. This study examines the roles of the AT1 receptor and CD44 gene expression in collagen synthesis through Ang II stimulated cardiac fibroblasts. Fibroblasts were isolated from the neonatal rat hearts;the activation of fibroblasts was evaluated using the assays of cell viability and migration, and silencing of CD44 gene expression was conducted with small interfering RNA (siRNA). Results showed that Ang II significantly increases the cell proliferation and migration in a dose-dependent manner. Upon activation, the protein levels of TGF-β1, Smad2, Smad4 and collagen I were significantly increased (all p < 0.05 vs. unstimulated cells), but these changes were significantly downregulated by the AT1 receptor blocker, telmisartan (all p < 0.05 vs. Ang II activated cells). Furthermore, mRNA and protein level of CD44 were upregulated, and there was a linear correlation between CD44 and TGF-β1 as demonstrated by Pearson correlation analysis (r = 0.955, p < 0.01). Gene transfection of fibroblasts with Ad-CD44 siRNA, as evidenced by low levels of CD44 mRNA and protein, significantly reduced the production of collagen I. In summary, these results indicate that the proliferation, migration and collagen production from Ang II activated cardiac fibroblasts are potentially mediated by the AT1 receptor and CD44. Such a signaling mechanism could be crucial for the production of collagen and the development of tissue fibrosis in the heart.展开更多
An analytical model has been developed for analyzing the braking torque in electromagnetic retarder by flux tube and armature reaction method. The magnetic field distribution in air gap, the eddy current induced in th...An analytical model has been developed for analyzing the braking torque in electromagnetic retarder by flux tube and armature reaction method. The magnetic field distribution in air gap, the eddy current induced in the rotor and the braking torque are calculated by the developed model. Two-dimensional and three-dimensional finite element models for retarder have also been developed. Results from the analytical model are compared with those from finite element models. The validity of these three models is checked by the comparison of the theoretical predictions and the measurements from an experimental prototype. The influencing factors of braking torque have been studied.展开更多
文摘Angiotensin II (Ang II) is known to elicit cardiac fibrosis by activating the AT1 receptor and CD44 expression in the in vivo model. However, the cellular/molecular mechanisms underlying cardiac fibrosis are still not well understood. This study examines the roles of the AT1 receptor and CD44 gene expression in collagen synthesis through Ang II stimulated cardiac fibroblasts. Fibroblasts were isolated from the neonatal rat hearts;the activation of fibroblasts was evaluated using the assays of cell viability and migration, and silencing of CD44 gene expression was conducted with small interfering RNA (siRNA). Results showed that Ang II significantly increases the cell proliferation and migration in a dose-dependent manner. Upon activation, the protein levels of TGF-β1, Smad2, Smad4 and collagen I were significantly increased (all p < 0.05 vs. unstimulated cells), but these changes were significantly downregulated by the AT1 receptor blocker, telmisartan (all p < 0.05 vs. Ang II activated cells). Furthermore, mRNA and protein level of CD44 were upregulated, and there was a linear correlation between CD44 and TGF-β1 as demonstrated by Pearson correlation analysis (r = 0.955, p < 0.01). Gene transfection of fibroblasts with Ad-CD44 siRNA, as evidenced by low levels of CD44 mRNA and protein, significantly reduced the production of collagen I. In summary, these results indicate that the proliferation, migration and collagen production from Ang II activated cardiac fibroblasts are potentially mediated by the AT1 receptor and CD44. Such a signaling mechanism could be crucial for the production of collagen and the development of tissue fibrosis in the heart.
基金supported by the National Natural Science Foundation of China(62005127)the Natural Science Foundation of Jiangsu Province(BK20200751)+2 种基金the Project of Jiangsu Specially-Appointed Professor(RK030STP22003)the Research Startup Fund of Nanjing University of Posts and Telecommunications(NY220068)the Project of State Key Laboratory of Organic Electronics and Information Displays(ZS030ZR22014).
文摘An analytical model has been developed for analyzing the braking torque in electromagnetic retarder by flux tube and armature reaction method. The magnetic field distribution in air gap, the eddy current induced in the rotor and the braking torque are calculated by the developed model. Two-dimensional and three-dimensional finite element models for retarder have also been developed. Results from the analytical model are compared with those from finite element models. The validity of these three models is checked by the comparison of the theoretical predictions and the measurements from an experimental prototype. The influencing factors of braking torque have been studied.