Date of Award

Spring 4-17-2023

Degree Type

Thesis

Degree Name

Master of Interdisciplinary Studies (MIS)

Department

Biomedical Sciences

First Advisor

Chunying Li

Second Advisor

Ping Song

Abstract

Background: Atherosclerosis is a chronic inflammatory condition that affects the arteries and is distinguished by the formation of plaques. This can lead to constricted blood flow and conceivably lethal cardiovascular events. The disease progressed over the years and is impacted by various risk factors, including high blood pressure, diabetes, smoking, obesity, and high cholesterol. Atherosclerosis contributes to a quarter of the world's deaths globally. Therefore, in this article, we put together an impartial, systematic, and organized bioinformatics system to understand the biomarkers and possible regulatory targets involved in treating Atherosclerosis and plaque development to understand better the disease's pathogenesis, which can help reduce the global risk of cardiovascular disease.

Material/Methods: Microarray datasets GSE43292 and GSE28829 were obtained from the Gene Expression Omnibus database (GEO). Limma analysis was done in R version 4.2.2 using the Bioconductor package version 3.16 by dividing GSE28829 into two groups, advanced and early plaque, to find the DEGS, whereas GSE43292 was divided into two groups, namely advanced plaque, and microscopically intact tissue to find the DEGS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these modules were performed by Enrichr. Differentially expressed genes (DEGs) were mapped into calcification-related genes using the STRING database; two PPI networks were generated. These PPI genes were used to extract. Transcription factors (Tf) from CHea3 and MiRNA from MIRwalk were sorted about Atherosclerosis to do the FFL analysis. Further experimental studies were done to verify the key miRNAs, i.e., that showed a strong association with the gene and transcription factor (TF).

Results: The genes were found in the DEGS list in GSE28829 and GSE43292. The PPI genes were identified as. GO and KEGG enrichment analysis revealed that genes in GSE28829 were enriched. At the same time, the genes in GSE43292 were enriched.

Conclusions: Overall, the DEG analysis of GSE28829 and GSE43292 provides insights into the molecular mechanisms underlying the progression of Atherosclerosis from early to advanced stages. The upregulation of genes involved in an extracellular matrix organization and adhesion and the downregulation of genes involved in immune and inflammatory responses suggest that changes in the plaque microenvironment may contribute to disease progression. These findings have important implications for the development of new therapeutic strategies for the treatment of Atherosclerosis

DOI

https://doi.org/10.57709/35539985

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