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Understanding the progression of atherosclerosis through gene profiling and co-expression network analysis in Apob(tm2Sgy)Ldlr(tm1Her) double knockout mice
Journal article   Open access   Peer reviewed

Understanding the progression of atherosclerosis through gene profiling and co-expression network analysis in Apob(tm2Sgy)Ldlr(tm1Her) double knockout mice

Vrushali Deshpande, Ankit Sharma, Rupak Mukhopadhyay, Lakshmi Narasimha Rao Thota, Madankumar Ghatge, Rajani Kanth Vangala, Vijay V Kakkar and Lakshmi Mundkur
Genomics (San Diego, Calif.), Vol.107(6), pp.239-247
06/2016
DOI: 10.1016/j.ygeno.2016.04.007
PMID: 27133569
url
https://doi.org/10.1016/j.ygeno.2016.04.007View
Published (Version of record) Open Access

Abstract

The objective of the study was to gain molecular insights into the progression of atherosclerosis in Apob(tm2Sgy)Ldlr(tm1Her) mice, using transcriptome profiles. Weighted gene co network analysis (WGCNA) and time course analysis using limma were used to study disease progression from 0 to 20weeks. Five co-expression modules were identified by WGCNA using the expression values of 2153 genes. Genes associated with autophagy, endoplasmic reticulum stress, inflammation and lipid metabolism were differentially expressed at early stages of atherosclerosis. Time course analysis highlighted activation of inflammatory gene signaling at 4weeks, cell proliferation and calcification at 8weeks, amyloid like structures and oxidative stress at 14weeks and enhanced production of inflammatory cytokines at 20weeks. Our results suggest that maximum gene perturbations occur during early atherosclerosis which could be the danger signals associated with subclinical disease. Understanding these genes and associated pathways can help in improvement of diagnostic and therapeutic targets for atherosclerosis.
Animals Apolipoproteins B - genetics Atherosclerosis - genetics Atherosclerosis - pathology Autophagy - genetics Disease Models, Animal Disease Progression Endoplasmic Reticulum Stress - genetics Gene Expression Regulation Gene Regulatory Networks Humans Inflammation - genetics Inflammation - pathology Lipid Metabolism - genetics Mice Mice, Knockout Oxidative Stress - genetics Receptors, LDL - drug effects

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