Atherosclerosis is a
vascular injury characterized by elevated tissue levels of
tumor necrosis factor-alpha (
TNF-alpha), increased expression of endothelial cell adhesion molecules, and vascular wall inflammatory cell infiltration. Foam cells are associated with
atherosclerotic plaque material, and
low density lipoprotein (
LDL) is a
lipid component of foam cells.
Malondialdehyde (MDA) is an oxidative product of
unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted)
proteins, including MDA-modified
LDL, are present in atherosclerotic human vascular tissue.
Acetaldehyde (AA) is the major metabolic product of
ethanol oxidation. Both MDA and AA are highly reactive
aldehydes and will combine with
proteins to produce an antigenically distinct
protein adduct, termed the MAA adduct. This study demonstrates that
proteins modified in the presence of high concentrations of MDA can produce MAA-modified
proteins in vitro. In addition, MAA adducted
proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release
TNF-alpha, and cause rHEC upregulation of endothelial adhesion molecule expression, including
ICAM-1. These adhesion molecules are required for circulating inflammatory cells to adhere to endothelium which allows inflammatory cell tissue infiltration. Additionally, MAA modified
proteins were defected in human atherosclerotic aortic vascular tissue but not in normal aortic tissue. Since
atherosclerosis is associated with an inflammatory
vascular injury characterized by elevated tissue
TNF-alpha concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted
proteins may be formed in
atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in
atherosclerosis. These data further suggest that previous studies demonstrating MDA modified
protein in
atherosclerotic plaque may in fact have MAA modified
proteins associated with them.