Macrophage p53 deficiency leads to enhanced atherosclerosis in APOE*3-Leiden transgenic mice

Circulation Research
Bart J M van VlijmenLouis M Havekes

Abstract

Cell proliferation and cell death (either necrosis or apoptosis) are key processes in the progression of atherosclerosis. The tumor suppressor gene p53 is an essential gene in cell proliferation and cell death and is upregulated in human atherosclerotic plaques, both in smooth muscle cells and in macrophages. In the present study, we investigated the importance of macrophage p53 in the progression of atherosclerosis using bone marrow transplantation in APOE*3-Leiden transgenic mice, an animal model for human-like atherosclerosis. APOE*3-Leiden mice were lethally irradiated and reconstituted with bone marrow derived from either p53-deficient (p53(-/-)) or control (p53(+/+)) donor mice. Reconstitution of mice with p53(-/-) bone marrow did not result in any hemopoietic abnormalities as compared with p53(+/+) transplanted mice. After 12 weeks on an atherogenic diet, APOE*3-Leiden mice reconstituted with p53(-/-) bone marrow showed a significant (P=0.006) 2.3-fold increase in total atherosclerotic lesion area as compared with mice reconstituted with p53(+/+) bone marrow. Although likely a secondary effect of the increased lesion area, p53(-/-) transplanted mice also showed significantly more lesion necrosis (necrotic index, 1.1+/-1....Continue Reading

References

Feb 11, 1988·Nucleic Acids Research·S A MillerH F Polesky
Dec 1, 1987·Atherosclerosis·B PaigenR A Williams
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·J D SmithM Miyata
Apr 1, 1994·The Journal of Clinical Investigation·B J van VlijmenL M Havekes
May 1, 1996·Genes & Development·L J Ko, C Prives
Oct 1, 1996·Haemostasis·V FusterJ T Fallon
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S FazioM F Linton
Aug 29, 1997·The Journal of Experimental Medicine·M P VierboomC J Melief
Dec 31, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R KinscherfJ Metz
May 3, 2000·The Journal of Biological Chemistry·P M Yao, I Tabas

❮ Previous
Next ❯

Citations

Aug 31, 2002·Environmental and Molecular Mutagenesis·Samantha ManfrediMaria Grazia Andreassi
Nov 11, 2009·Cardiovascular Research·José J FusterVicente Andrés
Sep 19, 2001·Current Opinion in Lipidology·W Martinet, M M Kockx
Sep 28, 2002·Current Opinion in Lipidology·Birgit C G FaberKitty B J M Cleutjens
Sep 12, 2012·Current Opinion in Lipidology·Vicente AndrésCarlos Silvestre-Roig
Jul 3, 2010·Cold Spring Harbor Perspectives in Biology·Andrei V Gudkov, Elena A Komarova
Oct 20, 2010·Molecular and Cellular Biology·Heather L ArmataHayla K Sluss
Aug 9, 2011·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Maziar RiazyUrs P Steinbrecher
Sep 20, 2012·International Journal of Inflammation·Nhat-Tu LeJun-Ichi Abe
Oct 23, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·June LiuMichael S Sinensky
Mar 30, 2013·Circulation Research·Mark W Feinberg
Jul 11, 2006·The Journal of Clinical Investigation·Clay F Semenkovich
Jul 23, 2011·Genes & Cancer·Andrei V GudkovElena A Komarova
Mar 9, 2010·Journal of Lipid Research·Babak RazaniClay F Semenkovich
Oct 28, 2008·Journal of Lipid Research·Tracie Seimon, Ira Tabas
Jan 28, 2003·Circulation Journal : Official Journal of the Japanese Circulation Society·Masao MoroiShigehiro Katayama
Jul 24, 2002·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hideki InadaHiroaki Matsuoka
Jan 22, 2014·Nature Communications·Michito HamadaSatoru Takahashi
Mar 13, 2012·Current Atherosclerosis Reports·Marten A HoeksemaMenno P J de Winther
Jun 1, 2011·The Journal of Cell Biology·Kyung-Sun HeoJun-ichi Abe
Jun 25, 2015·American Journal of Respiratory Cell and Molecular Biology·Sandra ChruscielLaurent Boyer
Jul 24, 2012·Trends in Endocrinology and Metabolism : TEM·Ido Goldstein, Varda Rotter
Jul 18, 2009·Atherosclerosis·Lianne S M BoestenMenno P J de Winther
Dec 10, 2015·Nature Medicine·Bennett G ChildsJan M van Deursen
Dec 25, 2007·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·George Tsirpanlis
Mar 27, 2007·Mutation Research·John MercerMartin Bennett
Jul 16, 2009·Journal of Cellular and Molecular Medicine·Lei ZhangYun Zhang
Oct 8, 2009·Journal of Clinical Pharmacology·Zhi-hao WangWei Zhang
Jun 27, 2006·International Journal of Cardiology·Moussa AlkhalafNabila Abdella
Feb 19, 2015·Journal of Biomedical Materials Research. Part a·Jung-Hee KimEunjoo Kim
Oct 30, 2012·Endocrine Research·Debra FranckHayla K Sluss
Apr 14, 2015·Seminars in Immunology·Joana Viola, Oliver Soehnlein
Apr 22, 2003·Progress in Cardiovascular Diseases·Xing Li WangJian Wang
Apr 25, 2012·International Journal of Cardiology·Aya MatsumotoJeff S Coombes
Nov 5, 2013·Cancer Biology & Therapy·Olga V LeontievaMikhail V Blagosklonny

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis