title: Homocysteine in microvascular endothelial cell barrier permeability.
abstract: Redox stress activates the endothelium and upregulates matrix metalloproteinases (MMPs), which degrade the matrix and lead to blood-endothelial barrier leakage. Interestingly, elevated levels of plasma homocysteine (Hcy) are associated with vascular dementia, seizure, stroke, and Alzheimer disease. Hcy competes with the gamma-aminobutyric acid (GABA)-A/B receptors and behave like an excitatory neurotransmitter. GABA stimulates the inhibitory neurotransmitter GABA-A/B receptor and decreases arterial blood pressure. However, the neural mechanisms of microvascular remodeling in hyperhomocysteinemia are unclear. This review addresses the idea that Hcy induces microvascular permeability by attenuating the GABA-A/B receptors and increasing redox stress, which activates a disintegrin and metalloproteinase that suppresses tissue inhibitors of metalloproteinase. This process causes disruption of the matrix in the blood-brain barrier. Understanding the mechanism of Hcy-mediated changes in permeability of the blood-brain barrier and extracellular matrix that can alter the neuronal environment in cerebral-vascular dementia is of great importance in developing treatments for this disease.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, A-1115, 500 South Preston Street, Louisville, KY 40202, USA. s0tyag01@louisville.edu
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
authors.forename: David
authors.initials: D
authors.lastname: Lominadze
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000378:metabolism*; D008833:Microcirculation / Q000378:metabolism*; D008955:Models, Cardiovascular; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism*
chemical_list: D006710:Homocysteine