The role of versican during development of heart failure
The purpose of the study is to understand the role of the proteoglycan versican during the development of heart failure. Versican is as an essential extracellular matrix component during cardiac development, while very few studies have shown upregulation of versican during the development of heart failure in adult mice. Thus, the specific function of versican in cardiac remodeling in adult mice remains unknown.
Due to poor prognosis of heart failure, it is crucial to understand the molecular mechanisms and identify a novel target for therapy. Since versican has not been studied during the development of heart failure, especially in adult mice and in patients, this project could reveal the potential use of versican as a novel therapeutic target for heart failure.
To study the role of versican in cardiac fibrosis induced by hypertension or valvular disease, the animals are subjected to aortic banding procedure. This will show whether the genetically modified mice have a heart failure phenotype compared to control mice, and provides a possibility to reveal the role of versican. The animals are sedated and anesthetized as per the standard protocol during the surgery (with 98.7% survival) and are very well taken care of after the surgery. The methods are well established at our research institute (IEMF) and are used frequently.
We shall use three lines of genetically modified mice, two lines will be used for generating a mouse line for inducible targeting of versican (5044 animals in total for this study). The number of mice needed has been determined from previous experience of the required animals to conduct the proposed experiments and the surgical procedures.
We actively use 3R in this proposal by using well-established methods for surgery at our institute, which improved the survival of animals and limits the number of animals used for experiments. We also use cell lines for in vitro studies to understand the mechanism or role of versican, thus minimizing the use of animals. However, animal models are essential to understand the role of a protein in vivo and develop it as a therapeutic target.
Due to poor prognosis of heart failure, it is crucial to understand the molecular mechanisms and identify a novel target for therapy. Since versican has not been studied during the development of heart failure, especially in adult mice and in patients, this project could reveal the potential use of versican as a novel therapeutic target for heart failure.
To study the role of versican in cardiac fibrosis induced by hypertension or valvular disease, the animals are subjected to aortic banding procedure. This will show whether the genetically modified mice have a heart failure phenotype compared to control mice, and provides a possibility to reveal the role of versican. The animals are sedated and anesthetized as per the standard protocol during the surgery (with 98.7% survival) and are very well taken care of after the surgery. The methods are well established at our research institute (IEMF) and are used frequently.
We shall use three lines of genetically modified mice, two lines will be used for generating a mouse line for inducible targeting of versican (5044 animals in total for this study). The number of mice needed has been determined from previous experience of the required animals to conduct the proposed experiments and the surgical procedures.
We actively use 3R in this proposal by using well-established methods for surgery at our institute, which improved the survival of animals and limits the number of animals used for experiments. We also use cell lines for in vitro studies to understand the mechanism or role of versican, thus minimizing the use of animals. However, animal models are essential to understand the role of a protein in vivo and develop it as a therapeutic target.