The aim of my project is to identify Cathepsin S inhibitors using in silico models and in vitro through fluorescence-based enzyme assay, and tissue culture.
Atherosclerosis is a chronic inflammatory disease that significant contributions to incidents of CVDs such as heart failure, stroke, and hypertension. It is caused by a high accumulation of low-density lipoprotein (LDL) in the subendothelial with subsequent LDL oxidation into oxLDLs, and high blood pressure activates endothelial cells, promotes the expression of adhesion molecules, and facilitates the migration of monocytes into the aortic wall. Again, Cathepsin S which is found in the spleen, macrophages, and lymph may act like matrix metalloproteinase and releases adhesion molecules.
Research on animal models of atherosclerosis has shown that cathepsin S deficiency resulted in smaller atherosclerotic plaques and reduced disruption of elastic fiber sheets within the tunica media. For the project, I have proposed to use RAW264.7 and Primary Human Aortic Endothelial Cells (HAoEC) cells.
Hello Sanele Khoza
You could develop co-culture models for atherosclerosis-associated studies. The co-culture systems include direct cell-to-cell and indirect transwell co-cultures. Various cell types involved in atherosclerosis pathology which include ECs, SMCs, and macrophages can be used in various direct and indirect co-culture studies to create blood vessels for examining inflammation and its role in atherosclerosis.
This type of co-culture system can help in the study of cell interaction and adhesion influenced by specific factors involved in the pathogenesis of atherosclerosis. You could also seed cells in 2D scaffolds or microfluidic chips for better mimicry of the physiology and pathology of atherosclerosis environment.
Please refer to the references I have attached below for more information. They may be helpful to establish the atherosclerosis model.
1. Article Co-culture Methods Used to Model Atherosclerosis In Vitro Us...
2. Article Recent Progress in in vitro Models for Atherosclerosis Studies
3. Article Reconstitution of the vascular wall in vitro. A novel model ...
Best.
Hello Malcolm Nobre
Thank you so much, I will look at this article and the approach this you've suggested.
Both RAW264.7 cells and Primary Human Aortic Endothelial Cells (HAoEC) are relevant cell lines to consider for studying atherosclerosis and evaluating the effects of Cathepsin S inhibitors. Here's a breakdown of their roles and suitability:
Using both RAW264.7 cells and Primary HAoEC in your project would provide a comprehensive understanding of the effects of Cathepsin S inhibitors on key cell types involved in atherosclerosis development. This approach allows you to examine the interplay between macrophages, foam cell formation, and endothelial dysfunction.
Remember to optimize culture conditions for these cell lines, such as appropriate media formulations and stimuli, to mimic the atherosclerotic environment as closely as possible. Additionally, it's important to consider the limitations of in vitro cell culture models and potentially validate your findings in animal models or ex vivo human tissues for a more comprehensive understanding of the therapeutic potential of Cathepsin S inhibitors in atherosclerosis.
Hello Saif Wahid
Thank you for the valuable information you provided. I greatly appreciate it and will definitely take it into consideration. Moving forward, our next course of action will involve validating our findings through experimentation using a rodent model.
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