Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery |
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| Institution: | 1. Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA 19107-5244;2. Department of Radiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX;3. Philips Healthcare, Cleveland, OH;1. Department of Analytical Biohemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan;2. Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya, Tokyo 156-8506, Japan;1. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA;2. San Mateo, CA, USA;3. Winston-Salem, NC, USA;1. Department of Neurosurgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;2. Department of Medical informatics & Integrative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;1. Department of Cardiology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey;2. Department of Cardiology, Ayd?n City Hospital, Aydin, Turkey;3. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Adnan Menderes University, Aydin, Turkey;4. Department of Histology and Embryology, Faculty of Veterinary Medicine, Adnan Menderes University, Aydin, Turkey;5. Department of Cardiology, Ada T?p Hospital, Sakarya, Turkey |
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| Abstract: | An elevated level of Homocysteine (Hcy) is a risk factor for vascular dementia and stroke. Cysthathionine β Synthase (CBS) gene is involved in the clearance of Hcy. Homozygous individuals for (CBS?/?) die early, but heterozygous for (CBS?/+) survive with high levels of Hcy. The γ-Amino Butyric Acid (GABA) presents in the central nervous system (CNS) and functions as an inhibitory neurotransmitter. Hcy competes with GABA at the GABAA receptor and affects the CNS function. We hypothesize that Hcy causes a decrease in blood flow to the brain due to increase in vascular resistance (VR) because of arterial remodeling in the carotid artery (CA). Blood pressure and blood flow in CA of wild type (WT), CBS?/+, CBS?/+ GABAA?/? double knockout, and GABAA?/? were measured. CA was stained with trichrome, and the brain permeability was measured. Matrix Metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-3, TIMP-4), elastin, and collagen-III expression were measured by real-time polymerase chain reaction (RT-PCR). Results showed an increase in VR in CBS?/+/GABAA?/?double knockout > CBS?/+/ > GABAA?/? compared to WT mice. Increased MMP-2, MMP-9, collagen-III and TIMP-3 mRNA levels were found in GABAA?/?, CBS?/+, CBS?/+/GABAA double knockout compared to WT. The levels of TIMP-4 and elastin were decreased, whereas the levels of MMP-2, MMP-9 and TIMP-3 increased, which indirectly reflected the arterial resistance. These results suggested that Hcy caused arterial remodeling in part, by increase in collagen/elastin ratio thereby increasing VR leading to the decrease in CA blood flow. |
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