Diabetes and diabetes-associated lipid abnormalities have distinct effects on initiation and progression of atherosclerotic lesions

The Journal of Clinical Investigation
Catherine B RenardKarin E Bornfeldt

Abstract

Diabetes in humans accelerates cardiovascular disease caused by atherosclerosis. The relative contributions of hyperglycemia and dyslipidemia to atherosclerosis in patients with diabetes are not clear, largely because there is a lack of suitable animal models. We therefore have developed a transgenic mouse model that closely mimics atherosclerosis in humans with type 1 diabetes by breeding low-density lipoprotein receptor-deficient mice with transgenic mice in which type 1 diabetes can be induced at will. These mice express a viral protein under control of the insulin promoter and, when infected by the virus, develop an autoimmune attack on the insulin-producing beta cells and subsequently develop type 1 diabetes. When these mice are fed a cholesterol-free diet, diabetes, in the absence of associated lipid abnormalities, causes both accelerated lesion initiation and increased arterial macrophage accumulation. When diabetic mice are fed cholesterol-rich diets, on the other hand, they develop severe hypertriglyceridemia and advanced lesions, characterized by extensive intralesional hemorrhage. This progression to advanced lesions is largely dependent on diabetes-induced dyslipidemia, because hyperlipidemic diabetic and nondiabeti...Continue Reading

References

May 11, 1979·JAMA : the Journal of the American Medical Association·W B Kannel, D L McGee
May 1, 1994·The Journal of Clinical Investigation·S IshibashiD K Burns
Sep 30, 1993·The New England Journal of Medicine·UNKNOWN Diabetes Control and Complications Trial Research GroupC Siebert
Apr 1, 1996·The Journal of Clinical Investigation·V V KunjathoorR C LeBoeuf
Sep 22, 1998·Arteriosclerosis, Thrombosis, and Vascular Biology·R S CrawfordA Chait
Nov 13, 1998·Current Opinion in Lipidology·K J Williams, I Tabas
Dec 8, 1998·American Heart Journal·R VirmaniA Farb
Dec 11, 1999·Arteriosclerosis, Thrombosis, and Vascular Biology·J L DixonM Sturek
Mar 24, 2000·Atherosclerosis·A G ZamanJ J Badimon
May 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·R VirmaniS M Schwartz
Dec 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·M E RosenfeldS M Schwartz
Jun 26, 2001·Diabetes·R G GerrityT Kimsey
May 15, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Helen WilliamsChristopher Langdale Jackson
Mar 5, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Paul CullenUNKNOWN MAFAPS Consortium
Sep 6, 2003·Frontiers in Bioscience : a Journal and Virtual Library·Stephen M Schwartz, Karin E Bornfeldt
Dec 4, 2003·Biochemical Society Transactions·A S JanuszewskiJ W Baynes
Dec 12, 2003·The New England Journal of Medicine·Frank D KolodgieRenu Virmani
Mar 17, 2004·Circulation·Riccardo CandidoKarin A Jandeleit-Dahm

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Citations

Sep 17, 2013·Current Atherosclerosis Reports·Ira J Goldberg, Karin E Bornfeldt
Feb 5, 2009·Current Diabetes Reports·Michelle M Averill, Karin E Bornfeldt
Jun 14, 2005·Diabetes Research and Clinical Practice·Rodney J DilleyPeter J Little
May 1, 2009·Nature Reviews. Drug Discovery·Nigel A CalcuttAnn Marie Schmidt
Feb 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Fredrik JohanssonKarin E Bornfeldt
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jenny E KanterKarin E Bornfeldt
Sep 29, 2009·The Journal of Biological Chemistry·Chongren TangJohn F Oram
Aug 8, 2013·Diabetes Technology & Therapeutics·Claudia EberleChristoph Ament
Sep 5, 2008·Current Opinion in Lipidology·Jan NilssonHarry Björkbacka
Nov 1, 2008·The Journal of Pharmacology and Experimental Therapeutics·Hye-Lim NohIra J Goldberg
Mar 24, 2009·Annual Review of Immunology·Elena Galkina, Klaus Ley
Oct 16, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Neeta AdhikariJennifer L Hall
Oct 12, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Chuchun L ChangRichard J Deckelbaum
Mar 3, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Godfrey S Getz, Catherine A Reardon
Aug 30, 2005·The Journal of Clinical Investigation·Reeba K VikramadithyanIra J Goldberg
Jan 30, 2010·Journal of Lipid Research·Deepa TanejaLisa R Tannock
Dec 8, 2009·Journal of Lipid Research·Chongren TangJohn F Oram
Nov 26, 2008·Journal of Lipid Research·Alan Chait, Karin E Bornfeldt
Feb 24, 2006·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Anna C Calkin, Terri J Allen
Nov 17, 2012·Trends in Endocrinology and Metabolism : TEM·Jenny E Kanter, Karin E Bornfeldt
Mar 9, 2006·Diabetes & Metabolism·C Renard, E Van Obberghen
Jun 11, 2011·Diabetic Medicine : a Journal of the British Diabetic Association·A S de M MatheusM B Gomes
Aug 17, 2005·Atherosclerosis·Marnie L GruenAlyssa H Hasty
Apr 20, 2010·Osteoarthritis and Cartilage·M J Martínez-CalatravaG Herrero-Beaumont
Feb 21, 2009·Journal of the American College of Cardiology·Gabriela Orasanu, Jorge Plutzky
Nov 8, 2011·Cell Metabolism·Karin E Bornfeldt, Ira Tabas
Oct 12, 2013·The American Journal of Pathology·Nathalie GaudreaultRobert L Raffai
Jul 5, 2011·The American Journal of Pathology·Joel ThompsonLisa R Tannock
Sep 30, 2010·Journal of Cardiovascular Disease Research·Ram K Mathur
Oct 30, 2014·Frontiers in Endocrinology·Sandra MerscherArmando J Mendez
May 23, 2014·Diabetes/metabolism Research and Reviews·Randhir SinghRakesh Gollen

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Methods Mentioned

BETA
transgenic
RIP
genotyping
ELISA

Software Mentioned

GraphPad Prism
SPSS
NIH Image
Image Pro - Plus
GraphPad
Adobe Photoshop

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