title: Understanding the progression of atherosclerosis through gene profiling and co-expression network analysis in Apob(tm2Sgy)Ldlr(tm1Her) double knockout mice.
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.
authors.affiliation: Molecular Immunology, Thrombosis Research Institute, Bangalore, India.
authors.forename: Vrushali
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Research Scholar, Manipal University, Thrombosis Research Institute, Bangalore, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Molecular Biology and Biotechnology, Tezpur University, Assam, India.
authors.forename: Rupak
authors.initials: R
authors.lastname: Mukhopadhyay
authors.affiliation: Research Scholar, Manipal University, Thrombosis Research Institute, Bangalore, India.
authors.forename: Lakshmi Narasimha Rao
authors.initials: LN
authors.lastname: Thota
authors.affiliation: Research Scholar, Manipal University, Thrombosis Research Institute, Bangalore, India.
authors.forename: Madankumar
authors.initials: M
authors.lastname: Ghatge
authors.affiliation: Bioinformatics and Biostatistics Unit, Thrombosis Research Institute, Bangalore, India.
authors.forename: Rajani Kanth
authors.initials: RK
authors.lastname: Vangala
authors.affiliation: Thrombosis Research Institute, Bangalore, India; Thrombosis Research Institute, London, UK.
authors.forename: Vijay V
authors.initials: VV
authors.lastname: Kakkar
authors.affiliation: Molecular Immunology, Thrombosis Research Institute, Bangalore, India. Electronic address: lakshmi.mundkur@triindia.org.in.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Mundkur
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D001343:Autophagy / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics; D011973:Receptors, LDL / Q000187:drug effects*
chemical_list: D001055:Apolipoproteins B; D011973:Receptors, LDL
keywords: Atherosclerosis; Disease progression; Endoplasmic reticulum stress; Inflammation; Weighted gene co-expression network analysis