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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #195871
Title: HOMOCYSTEINE INDUCED ATHEROSCLEROSIS DOES NOT DEPEND ON PROINFLAMMATORY CYTOKINES AND CHEMOKINES

Author
item THAMPI, PRAJITHA - ACNC/UAMS
item STEWART, BRAD - ACNC
item BADGER, THOMAS - ACNC/UAMS
item NAGARAJAN, SHANMUGAM - ACNC/UAMS

Submitted to: American Association of Immunologists Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 3/29/2006
Publication Date: 5/12/2006
Citation: Thampi, P., Stewart, B., Badger, T.M., Nagarajan, S. 2006. Homocysteine induced atherosclerosis does not depend on proinflammatory cytokines and chemokines [abstract]. In: Late Breaking Abstracts of The American Association of Immunologists, May 12-16, 2006, Boston, Massachusetts. p. 20.

Interpretive Summary: Atherosclerosis is a condition when fat deposits on the walls of blood vessels, causing them to thicken. This can prevent blood flow to heart causing an heart attack. Inflammation is the process by which our bodies respond to injury. Earlier studies have shown that atherosclerosis causes an inflammatory response. Several factors like high blood pressure, high fat content in diet, diabetes, and also increase in blood levels of an amino acid called homocysteine (Hcy) can cause atherosclerosis. Hcy is produced in our body from breaking down of the amino acid methionine. Our bodies receive methionine from eating meat, change in the enzymes required for its break down, and in vitamin deficiencies. By knowing how Hcy can cause atherosclerosis we can develop ways to prevent it. Our results show that increased Hcy levels causes thickening of arteries and also an inflammatory response.

Technical Abstract: Elevated plasma homocysteine (Hcy) levels are recognized as risk factors for cardio- and cerebrovascular diseases. ApoE mice fed with Hcy have increased cholesterol and aortic lesions, but underlying mechanisms need to be delineated. Hcy forms protein adducts and triggers immune activation. In ApoE-/- mice prone to atherosclerosis and elevated levels of low density lipoprotein (LDL), we hypothesized that elevated LDL promotes formation of homocystamide LDL (HcyLDL) adducts and that an immune response is generated. Mice were fed a standard chow (ND) or ND with 0.09%Hcy (High HCY (HHcy)) supplementation in drinking water. ELISA assays for Hcy modified proteins and HcyLDL in the sera showed presence of these modifications, with no significant differences between the groups. Immune activation analyzed by ELISA did not show any marked elevation in the HHcy group. Detailed lipid analysis of sera entailing cholesterol, triglycerides, high density lipoprotein (HDL) and LDL showed no significant change between the groups despite increased aortic lesions in HHcy animals. Similarly Real Time PCR did not demonstrate any significant induction of TNF-u, IL-1u, MCP-1 or RANTES genes in the macrophages from the HHcy group. Lesion analysis does prove that Hcy accelerates preexisting atheropathology in ApoE-/- mice, though the mechanism proposed is not supported by these results. Further studies are needed to determine the underlying mechanism by the Hcy-induced pathway of atherosclerosis.