title: Hexim1 heterozygosity stabilizes atherosclerotic plaque and decreased steatosis in ApoE null mice fed atherogenic diet.
abstract: Hexim-1 is an inhibitor of RNA polymerase II transcription elongation. Decreased Hexim-1 expression in animal models of chronic diseases such as left ventricular hypertrophy, obesity and cancer triggered significant changes in adaptation and remodeling. The main aim of this study was to evaluate the role of Hexim1 in lipid metabolism focused in the progression of atherosclerosis and steatosis. We used the C57BL6 apolipoprotein E (ApoE null) crossed bred to C57BL6Hexim1 heterozygous mice to obtain ApoE null - Hexim1 heterozygous mice (ApoE-HT). Both ApoE null backgrounds were fed high fat diet for twelve weeks. Then, we evaluated lipid metabolism, atherosclerotic plaque formation and liver steatosis. In order to understand changes in the transcriptome of both backgrounds during the progression of steatosis, we performed Affymetrix mouse 430 2.0 microarray. After 12 weeks of HFD, ApoE null and ApoE-HT showed similar increase of cholesterol and triglycerides in plasma. Plaque composition was altered in ApoE-HT. Additionally, liver triglycerides and steatosis were decreased in ApoE-HT mice. Affymetrix analysis revealed that decreased steatosis might be due to impaired inducible SOCS3 expression in ApoE-HT mice. In conclusion, decreased Hexim-1 expression does not alter cholesterol metabolism in ApoE null background after HFD. However, it promotes stable atherosclerotic plaque and decreased steatosis by promoting the anti-inflammatory TGFβ pathway and blocking the expression of the inducible and pro-inflammatory expression of SOCS3 respectively.
authors.affiliation: Department of Biological Sciences, State University of New York, College at Old Westbury, Old Westbury, New York 11568, USA.
authors.forename: Manya
authors.initials: M
authors.lastname: Dhar-Mascareno
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Rozenberg
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA.
authors.forename: Jahangir
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA.
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA; Departments of Surgery, Medicine and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Beckles
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA. Electronic address: emascareno@downstate.edu.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mascareno
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D004036:Diet, Atherogenic / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; C118642:Hexim1 protein, mouse; C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; D016601:RNA-Binding Proteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D014157:Transcription Factors; D002784:Cholesterol
keywords: Atherosclerosis; Hexim1; High fat diet; SOCS3; Smooth muscle α-actin; Steatosis; Triglycerides; miR145