Aspirin and pravastatin reduce lectin-like oxidized low density lipoprotein receptor-1 expression, adhesion molecules and oxidative stress in human coronary artery endothelial cells.
BACKGROUND
Oxidative stress and inflammation are important steps in the pathogenesis of atherosclerosis. We postulated that therapeutic concentrations of aspirin and pravastatin, especially in combination, may suppress oxidative stress and inflammation in endothelial cells, and this concept was examined in human coronary artery endothelial cells (HCAECs).


METHODS
Human coronary artery endothelial cells were cultured and treated with oxidized-low density lipoprotein (ox-LDL, 60 microg/ml for 24 hours) alone, or pre-treated with aspirin (1, 2 or 5 mmol/L), pravastatin (1, 5 or 10 micromol/L) or their combination (1 mmol/L aspirin and 5 micromol/L pravastatin), followed by ox-LDL treatment. After respective treatment, superoxide anion production, p38 mitogen activated protein kinase and transcription factor NF-kappaB activation, protein expression of lectin-like ox-LDL receptor-1 (LOX-1) and adhesion molecules, and monocyte adhesion were measured.


RESULTS
Ox-LDL treatment greatly elicited its receptor LOX-1 expression, superoxide anion production and inflammatory response, which were minimally affected by low concentration of aspirin (1 mmol/L) or pravastatin (5 micromol/L), but were markedly decreased by their combination. Activation of p38 mitogen activated protein kinase and NF-kappaB, the expression of intercellular adhesion molecule-1 and monocyte chemotactic protein-1, which were only mildly affected by aspirin or pravastatin alone, were significantly attenuated by their combination. As a consequence, monocyte adhesion to endothelial cells was markedly attenuated by the combination of the two agents. Well-known anti-oxidants alpha-tocopherol and gamma-tocopherol had similar inhibitory effects on ox-LDL-mediated oxidative stress and LOX-1 expression as well as monocyte adhesion as did the combination of aspirin and pravastatin.


CONCLUSIONS
These studies point to a positive interaction between aspirin and pravastatin with regard to endothelial biology. Anti-oxidant and subsequent anti-inflammatory effect may be one of the potential underling mechanisms.
Chen
Jia-wei
JW
Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Zhou
Shi-bei
SB
Tan
Zhi-ming
ZM
D000924:Anticholesteremic Agents / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017035:Pravastatin / Q000494:pharmacology*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D000924:Anticholesteremic Agents; D015815:Cell Adhesion Molecules; D016861:Cyclooxygenase Inhibitors; D051127:Scavenger Receptors, Class E; D013481:Superoxides; D017035:Pravastatin; D001241:Aspirin