Elevated levels of homocysteine compromise blood-brain barrier integrity in mice

Collaboration HS. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288: 2015-2022. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Br Med J. 2002;325: 1202. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346: 476-483. Watanabe M, Osada J, Aratani Y, et al. Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci U S A. 1995;92: 1585-1589. Frenette PS, Moyna C, Hartwell DW, Lowe JB, Hynes RO, Wagner DD. Platelet-endothelial interactions in inflamed mesenteric venules. Blood. 1998;91: 1318-1324. Smith ML, Smith MJ, Lawrence MB, Ley K. Viscosity-independent velocity of neutrophils rolling on p-selectin in vitro or in vivo. Microcirculation. 2002;9: 523-536. Methia N, Andre P, Hafezi-Moghadam A, Economopoulos M, Thomas KL, Wagner DD. ApoE deficiency compromises the blood brain barrier especially after injury. Mol Med. 2001;7: 810-815. Faraci FM, Lentz SR. Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke. 2004;35: 345-347. Fu WY, Dudman NP, Perry MA, Wang XL. Leukocytes extravasation in acute homocysteinemic rats. Atherosclerosis. 2002;161: 177-183. Pruefer D, Scalia R, Lefer AM. Homocysteine provokes leukocyte-endothelium interaction by downregulation of nitric oxide. Gen Pharmacol. 1999;33: 487-498. Weiss N, Heydrick S, Zhang YY, Bierl C, Cap A, Loscalzo J. Cellular redox state and endothelial dysfunction in mildly hyperhomocysteinemic cystathionine beta-synthase-deficient mice. Arterioscler Thromb Vasc Biol. 2002;22: 34-41. Matsushita K, Morrell CN, Cambien B, et al. Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor. Cell. 2003;115: 139-150. Del Maschio A, De Luigi A, Martin-Padura I, et al. Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM). J Exp Med. 1999;190: 1351-1356. van de Laak MF, Grobbee DE, van der Griend R, et al. A 2-step strategy to reduce the need for methionine-loading tests to diagnose hyperhomocysteinemia. J Lab Clin Med. 2003;142: 121-127. Wang G, Woo CW, Sung FL, Siow YL, O K. Increased monocyte adhesion to aortic endothelium in rats with hyperhomocysteinemia: role of chemokine and adhesion molecules. Arterioscler Thromb Vasc Biol. 2002;22: 1777-1783. Heydrick SJ, Weiss N, Thomas SR, et al. L-Homocysteine and L-homocystine stereospecifically induce endothelial nitric oxide synthase-dependent lipid peroxidation in endothelial cells. Free Radic Biol Med. 2004;36: 632-640. Lehmann M, Regland B, Blennow K, Gottfries CG. Vitamin B12-B6-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment. Dement Geriatr Cogn Disord. 2003;16: 145-150. Fullerton SM, Shirman GA, Strittmatter WJ, Matthew WD. Impairment of the blood-nerve and blood-brain barriers in apolipoprotein e knockout mice. Exp Neurol. 2001;169: 13-22. Mulder M, Blokland A, van den Berg DJ, et al. Apolipoprotein E protects against neuropathology induced by a high-fat diet and maintains the integrity of the blood-brain barrier during aging. Lab Invest. 2001;81: 953-960. Casserly I, Topol E. Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. Lancet. 2004;363: 1139-1146. Nag S. The Blood Brain Barrier: Biology and Research Protocols (Methods in Molecular Medicine). Totowa, NJ: Humana Press; 2003. Dayal S, Arning E, Bottiglieri T, et al. Cerebral vascular dysfunction mediated by superoxide in hyperhomocysteinemic mice. Stroke. 2004;35: 1957-1962. Di Simone N, Maggiano N, Caliandro D, et al. Homocysteine induces trophoblast cell death with apoptotic features. Biol Reprod. 2003;69: 1129-1134. Hossain GS, van Thienen JV, Werstuck GH, et al. TDAG51 is induced by homocysteine, promotes detachment-mediated programmed cell death, and contributes to the development of atherosclerosis in hyperhomocysteinemia. J Biol Chem. 2003;278: 30317-30327. Outinen PA, Sood SK, Pfeifer SI, et al. Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells. Blood. 1999;94: 959-967. Kaufman RJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest. 2002;110: 1389-1398. Kranich O, Dringen R, Sandberg M, Hamprecht B. Utilization of cysteine and cysteine precursors for the synthesis of glutathione in astroglial cultures: preference for cystine. Glia. 1998;22: 11-18. Nedergaard M, Ransom B, Goldman SA. New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 2003;26: 523-530. Wardlaw JM, Sandercock PA, Dennis MS, Starr J. Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia? Stroke. 2003;34: 806-812. Hofmann MA, Lalla E, Lu Y, et al. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest. 2001;107: 675-683. Zhou J, Moller J, Danielsen CC, et al. Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21: 1470-1476. Wang H, Jiang X, Yang F, et al. Hyperhomocysteinemia accelerates atherosclerosis in cystathionine beta-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation. Blood. 2003;101: 3901-3907.