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Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
In silico based analysis to explore genetic linkage between atherosclerosis and its potential risk factors
Hossain Mohammad Hridoy1, Md Nasim Haidar2, Chadni Khatun3,1
1Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.
Insights
This study identifies key molecular biomarkers and pathways involved in atherosclerosis (ATH) development. Findings aid in understanding ATH mechanisms and developing novel therapeutic targets for this cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Systems Biology
- Molecular Medicine
Background:
- Atherosclerosis (ATH) is a leading cause of mortality, driven by arterial plaque formation.
- Despite advances, residual threats persist due to unidentified therapeutic targets.
- Risk factors like hyperlipidemia, obesity, and hypertension significantly contribute to ATH progression.
Purpose of the Study:
- To identify molecular biomarkers for atherosclerosis onset and progression using a systems biology approach.
- To analyze gene expression data from tissues affected by various ATH risk factors.
- To uncover novel therapeutic targets by understanding underlying molecular mechanisms.
Main Methods:
- Analysis of microarray gene expression datasets from atherosclerosis and related risk factor tissues.
- Bioinformatic analyses including Protein-Protein Interaction (PPI), Gene Ontology (GO), and KEGG pathway analysis.
- Identification of differentially expressed genes (DEGs), hub proteins, transcription factors, and microRNAs (miRNAs).
Main Results:
- Identified key signaling pathways: chemokine signaling, cytokine-cytokine receptor interaction, cytosolic DNA-sensing, PPAR signaling, and NF-kappa B signaling.
- Discovered ten hub proteins (e.g., CCL5, TLR1, TNF) and five transcription factors (e.g., YY1, SRF).
- Pinpointed five significant miRNAs (e.g., mir-27a-3p, mir-16-5p) associated with atherosclerosis.
Conclusions:
- The identified molecular biomarkers and pathways offer insights into atherosclerosis mechanisms.
- Findings highlight potential targets for novel therapeutic strategies against atherosclerosis.
- Understanding the link between risk factors and molecular changes is crucial for future interventions.
Abstract:
Atherosclerosis (ATH) is a chronic cardiovascular disease characterized by plaque formation in arteries, and it is a major cause of illness and death. Although therapeutic advances have significantly improved the prognosis of ATH, missing therapeutic targets pose a significant residual threat. This research used a systems biology approach to identify the molecular biomarkers involved in the onset and progression of ATH, analysing microarray gene expression datasets from ATH and tissues impacted by risk factors such as high cholesterol, adipose tissue, smoking, obesity, sedentary lifestyle, stress, alcohol consumption, hypertension, hyperlipidaemia, high fat, diabetes to find the differentially expressed genes (DEGs). Bioinformatic analyses of Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted on differentially expressed genes, revealing metabolic and signaling pathways (the chemokine signaling pathway, cytokine-cytokine receptor interaction, the cytosolic DNA-sensing pathway, the peroxisome proliferator-activated receptors signaling pathway, and the nuclear factor-kappa B signaling pathway), ten hubs proteins (CCL5, CCR1, TLR1, CCR2, FCGR2A, IL1B, CD163, AIF1, CXCL-1 and TNF), five transcription factors (YY1, FOXL1, FOXC1, SRF, and GATA2), and five miRNAs (mir-27a-3p, mir-124-3p, mir-16-5p, mir-129-2-3p, mir-1-3p). These findings identify potential biomarkers that may increase knowledge of the mechanisms underlying ATH and their connection to risk factors, aiding in the development of new therapies.
