Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease

Cell Death and Differentiation
Richard C AustinGeoff H Werstuck

Abstract

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease, including ischemic heart disease, stroke, and peripheral vascular disease. Mutations in the enzymes responsible for homocysteine metabolism, particularly cystathionine beta-synthase (CBS) or 5,10-methylenetetrahydrofolate reductase (MTHFR), result in severe forms of HHcy. Additionally, nutritional deficiencies in B vitamin cofactors required for homocysteine metabolism, including folic acid, vitamin B6 (pyridoxal phosphate), and/or B12 (methylcobalamin), can induce HHcy. Studies using animal models of genetic- and diet-induced HHcy have recently demonstrated a causal relationship between HHcy, endothelial dysfunction, and accelerated atherosclerosis. Dietary enrichment in B vitamins attenuates these adverse effects of HHcy. Although oxidative stress and activation of proinflammatory factors have been proposed to explain the atherogenic effects of HHcy, recent in vitro and in vivo studies demonstrate that HHcy induces endoplasmic reticulum (ER) stress, leading to activation of the unfolded protein response (UPR). This review summarizes the current role of HHcy in endothelial dysfunction and explores the cellular mechanisms, including ER stress,...Continue Reading

References

Aug 1, 1992·Annals of Plastic Surgery·S E Mackinnon, G A Patterson
Apr 25, 1991·The New England Journal of Medicine·R ClarkeI Graham
Nov 1, 1989·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·D Reichl, N E Miller
Apr 1, 1986·The Journal of Clinical Investigation·G Starkebaum, J M Harlan
Jun 1, 1995·Circulation·J M IsnerJ Passeri
Feb 2, 1995·The New England Journal of Medicine·J SelhubI H Rosenberg
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·M WatanabeN Maeda
Mar 1, 1994·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·D G FrankenP W Kloppenborg
Dec 8, 1993·JAMA : the Journal of the American Medical Association·J SelhubI H Rosenberg
Sep 1, 1993·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·R H FryerG M Rodgers
Jan 12, 1996·The Journal of Biological Chemistry·Y R ChenT H Tan
Mar 21, 1996·The New England Journal of Medicine·M den HeijerF R Rosendaal
Apr 1, 1996·Nature Medicine·K S McCully
Dec 1, 1996·The Journal of Pathology·L HegyiM J Mitchinson
Jul 4, 1997·The Journal of Biological Chemistry·G R UpchurchJ Loscalzo
Nov 14, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·R T Lee, P Libby
Nov 14, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·A MajorsE H Pezacka
Dec 31, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·S R LentzD D Heistad
Apr 16, 1998·The New England Journal of Medicine·G N Welch, J Loscalzo
May 13, 1998·The Biochemical Journal·P A OutinenR C Austin
Jan 14, 1999·The New England Journal of Medicine·R Ross
Jul 10, 1999·Journal of the American College of Cardiology·P AmbrosiR Luccioni
Jul 31, 1999·Journal of Neurochemistry·I GomesM R Rosner
Dec 14, 1999·Mammalian Genome : Official Journal of the International Mammalian Genome Society·D FrankB Tycko

❮ Previous
Next ❯

Citations

Aug 2, 2008·Journal of Applied Genetics·Elisabetta Trabetti
Aug 7, 2009·Journal of Neural Transmission·Thomas Müller, Siegfried Muhlack
Apr 8, 2011·Amino Acids·Nele KanzelmeyerThomas Lücke
Jun 2, 2009·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Giuseppe SalemiI Lupo
Jul 18, 2012·Bulletin of Experimental Biology and Medicine·A V IvanovA A Kubatiev
Mar 8, 2008·Langmuir : the ACS Journal of Surfaces and Colloids·Arther T GatesIsiah M Warner
Sep 2, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Arther T GatesIsiah M Warner
Aug 17, 2006·Proceedings of the National Academy of Sciences of the United States of America·Peter S GargalovicAldons J Lusis
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lingfang ZengQingbo Xu
Sep 8, 2007·Antioxidants & Redox Signaling·Edith LubosDiane E Handy
Oct 17, 2007·Antioxidants & Redox Signaling·Jeffrey G DickhoutRichard C Austin
Sep 1, 2007·Antioxidants & Redox Signaling·Alla V Glushchenko, Donald W Jacobsen
Jan 8, 2009·Antioxidants & Redox Signaling·Joern R SteinertGiovanni E Mann
Nov 19, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·J Christopher StatesAaron Barchowsky
Jun 30, 2007·Cephalalgia : an International Journal of Headache·L M Cupini, E Stipa
Jul 20, 2006·Annual Review of Nutrition·Michiel P C SiroenPaul A M van Leeuwen
Jun 24, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Sanjana DayalSteven R Lentz
May 29, 2009·American Journal of Physiology. Renal Physiology·Utpal SenSuresh C Tyagi
Dec 2, 2010·Cardiovascular Diabetology·Vasundhara KainSandhya L Sitasawad
Mar 30, 2012·PloS One·Abdelmajid EloualidHassan Rouba
Oct 4, 2005·Clinical Chemistry and Laboratory Medicine : CCLM·Ciriaco CarruPaolo Porcu
Oct 4, 2005·Clinical Chemistry and Laboratory Medicine : CCLM·Donald W JacobsenJohn C Barbato
Oct 4, 2005·Clinical Chemistry and Laboratory Medicine : CCLM·Wolfgang HerrmannMuhidien Jouma
Jul 11, 2009·Journal of Clinical Biochemistry and Nutrition·Xu-Mei ZhangJohn X Wilson
Apr 16, 2013·Antioxidants & Redox Signaling·Sarathi ManiRui Wang
Oct 12, 2012·Journal of Advanced Pharmaceutical Technology & Research·Ankur RohillaRazia Khanam
Oct 23, 2008·Cell and Tissue Research·Wineke BakkerVictor W M van Hinsbergh
Sep 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Roberta d'Emmanuele di Villa BiancaRaffaella Sorrentino
Nov 26, 2011·Expert Review of Clinical Pharmacology·Yi-Hong LiuJin-Song Bian
Jan 23, 2015·International Journal of Molecular Sciences·Sudhakar Veeranki, Suresh C Tyagi

❮ Previous
Next ❯

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