Hexim1 heterozygosity stabilizes atherosclerotic plaque and decreased steatosis in ApoE null mice fed atherogenic diet. 2017

Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
Department of Biological Sciences, State University of New York, College at Old Westbury, Old Westbury, New York 11568, USA.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004036 Diet, Atherogenic A diet that contributes to the development and acceleration of ATHEROGENESIS. Atherogenic Diet,Atherogenic Diets,Diets, Atherogenic
D005234 Fatty Liver Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS. Liver Steatosis,Steatohepatitis,Steatosis of Liver,Visceral Steatosis,Liver Steatoses,Liver, Fatty,Steatohepatitides,Steatoses, Liver,Steatoses, Visceral,Steatosis, Liver,Steatosis, Visceral,Visceral Steatoses
D006579 Heterozygote An individual having different alleles at one or more loci regarding a specific character. Carriers, Genetic,Genetic Carriers,Carrier, Genetic,Genetic Carrier,Heterozygotes
D000071223 Suppressor of Cytokine Signaling 3 Protein A suppressor of cytokine signaling protein that consists of an N-terminal kinase-inhibitory region, a central SH2 DOMAIN, a characteristic C-terminal SOCS box (a 40-amino acid motif, which functions to recruit E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES). SOCS3 inhibits cytokine signaling by binding to RECEPTOR PROTEIN-TYROSINE KINASES as well as CYTOKINE RECEPTOR GP130; ERYTHROPOIETIN RECEPTORS; INSULIN RECEPTOR; and the LEPTIN RECEPTOR. Its functions include suppression of ERYTHROPOIESIS in the fetal liver. SOCS3 Protein,Suppressor of Cytokine Signaling Protein 3,Protein, SOCS3
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001013 Aorta, Thoracic The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA. Aorta, Ascending,Aorta, Descending,Aortic Arch,Aortic Root,Arch of the Aorta,Descending Aorta,Sinotubular Junction,Ascending Aorta,Thoracic Aorta,Aortic Roots,Arch, Aortic,Ascending Aortas,Junction, Sinotubular,Root, Aortic,Sinotubular Junctions
D001057 Apolipoproteins E A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III. Apo-E,Apo E,Apo E Isoproteins,ApoE,Apolipoprotein E Isoproteins,Apoprotein (E),Apoproteins E,Isoproteins, Apo E,Isoproteins, Apolipoprotein E

Related Publications

Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
December 2009, Medicine and science in sports and exercise,
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
January 2023, Frontiers in cell and developmental biology,
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
May 2017, Nutrition (Burbank, Los Angeles County, Calif.),
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
September 2015, Scientific reports,
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
January 2017, Journal of vascular research,
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
May 2021, International journal of molecular sciences,
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
August 2008, European journal of pharmacology,
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
October 2013, Molecular nutrition & food research,
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
June 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons,
Manya Dhar-Mascareno, and Inna Rozenberg, and Jahangir Iqbal, and M Mahmood Hussain, and Daniel Beckles, and Eduardo Mascareno
September 2006, Journal of the College of Physicians and Surgeons--Pakistan : JCPSP,
Copied contents to your clipboard!