Objective: To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats...Objective: To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the effects of three kinds of adrenergic receptor blockers: Carvedilol (CAR) , Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypertrophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA)was used in this study. Thirty two male wistar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER. Hemodynamics, ventricular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ / Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ /Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ /Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was independent of beta-adrenergic receptor antagonist.展开更多
In this paper, a nonautonomous stochastic food-chain system with functional response and impulsive perturbations is studied. By using Ito＇s formula, exponential martingale inequality, differential inequality and othe...In this paper, a nonautonomous stochastic food-chain system with functional response and impulsive perturbations is studied. By using Ito＇s formula, exponential martingale inequality, differential inequality and other mathematical skills, some sufficient conditions for the extinction, nonpersistence in the mean, persistence in the mean, and stochastic permanence of the system are established. Furthermore, some asymptotic properties of the solutions are also investigated. Finally, a series of numerical examples are presented to support the theoretical results, and effects of different intensities of white noises perturbations and impulsive effects are discussed by the simu｜ations.展开更多
Tolerance to nitroglycerin(GTN)greatly limits its long-time application,and the underlying mechanism remains largely unexplored.In the present study,we aimed to investigate the comprehensive changes in the transcripto...Tolerance to nitroglycerin(GTN)greatly limits its long-time application,and the underlying mechanism remains largely unexplored.In the present study,we aimed to investigate the comprehensive changes in the transcriptome of rat aorta tolerant to GTN by analyzing lncRNA expression.We employed the RNA sequencing(RNA-seq)technique to identify mRNAs and lncRNAs.Ingenuity pathway analysis(IPA)was used for pathway and functional analysis.RT-qPCR was used to validate the RNA-seq results.We identified 22788 genes(reads per kilobase million[RPKM]>0.1,14720 protein-coding genes and 4408 lncRNAs),including 115 differentially expressed(DE)mRNAs(65 up-regulated and 50 down-regulated)and 104 DE lncRNAs(56 up-regulated and 48 down-regulated),in GTN-tolerant aortas.IPA revealed the inhibition of a canonical pathway“Signaling by Rho Family GTPases”and alteration in six upstream regulators.Functional analysis showed that 11 genes were related to“disorder of blood pressure”.We predicted the cis-target genes of DE lncRNAs by the analysis of their neighboring genes.The results revealed the 28 DE lncRNAs adjacent to the 26 protein-coding genes.Many DE mRNAs and cis-target genes of DE lncRNAs have been implicated in the regulation of blood pressure or cell contraction.These results suggested that the dysregulated mRNAs and lncRNAs contributed to the development of GTN tolerance and could serve as potential targets to prevent and reverse GTN tolerance.展开更多
文摘Objective: To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the effects of three kinds of adrenergic receptor blockers: Carvedilol (CAR) , Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypertrophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA)was used in this study. Thirty two male wistar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER. Hemodynamics, ventricular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ / Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ /Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ /Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was independent of beta-adrenergic receptor antagonist.
基金Acknowledgments The authors would like to thank the editors and the anonymous referees for their helpful suggestions and comments which led to the improvement of our original manuscript. This work is supported by the National Natural Science Foundation of China （11372294 and 11261017）, Scientific Research Fund of Sichuan Provincial Education Department （14ZB0115 and 15ZB0113）, Zhejiang Provincial Natural Science Foundation （LQ13A010023） and Doctorial Research Fund of Southwest University of Science and Technology （15zx7138）.
文摘In this paper, a nonautonomous stochastic food-chain system with functional response and impulsive perturbations is studied. By using Ito＇s formula, exponential martingale inequality, differential inequality and other mathematical skills, some sufficient conditions for the extinction, nonpersistence in the mean, persistence in the mean, and stochastic permanence of the system are established. Furthermore, some asymptotic properties of the solutions are also investigated. Finally, a series of numerical examples are presented to support the theoretical results, and effects of different intensities of white noises perturbations and impulsive effects are discussed by the simu｜ations.
基金Scientific Research Fund of Hunan Provincial Education Department(Grant No.17B188,18A490)。
文摘Tolerance to nitroglycerin(GTN)greatly limits its long-time application,and the underlying mechanism remains largely unexplored.In the present study,we aimed to investigate the comprehensive changes in the transcriptome of rat aorta tolerant to GTN by analyzing lncRNA expression.We employed the RNA sequencing(RNA-seq)technique to identify mRNAs and lncRNAs.Ingenuity pathway analysis(IPA)was used for pathway and functional analysis.RT-qPCR was used to validate the RNA-seq results.We identified 22788 genes(reads per kilobase million[RPKM]>0.1,14720 protein-coding genes and 4408 lncRNAs),including 115 differentially expressed(DE)mRNAs(65 up-regulated and 50 down-regulated)and 104 DE lncRNAs(56 up-regulated and 48 down-regulated),in GTN-tolerant aortas.IPA revealed the inhibition of a canonical pathway“Signaling by Rho Family GTPases”and alteration in six upstream regulators.Functional analysis showed that 11 genes were related to“disorder of blood pressure”.We predicted the cis-target genes of DE lncRNAs by the analysis of their neighboring genes.The results revealed the 28 DE lncRNAs adjacent to the 26 protein-coding genes.Many DE mRNAs and cis-target genes of DE lncRNAs have been implicated in the regulation of blood pressure or cell contraction.These results suggested that the dysregulated mRNAs and lncRNAs contributed to the development of GTN tolerance and could serve as potential targets to prevent and reverse GTN tolerance.
