© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Infection and Inflammation Induce LDL Oxidation In Vivo
From the Departments of Medicine (R.A.M., M.N., A.H.M., K.R.F., C.G.), Surgery (I.S.) and Dermatology (W.M.H., Y.U.), University of California San Francisco, Calif, and Metabolism Section (R.A.M., M.N., A.H.M., K.R.F., C.G.), Medical Service, Department of Veterans Affairs Medical Center, San Francisco, Calif.
Correspondence to Riaz A. Memon, PhD, Department of Veterans Affairs Medical Center, Metabolism Section (111F), 4150 Clement St, San Francisco, CA 94121. E-mail rmemon{at}itsa.ucsf.edu
Abstract—Epidemiological studies have shown an increased incidence of coronary artery disease in patients with chronic infections and inflammatory disorders. Because oxidative modification of lipoproteins plays a major role in atherosclerosis, the present study was designed to test the hypothesis that the host response to infection and inflammation induces lipoprotein oxidation in vivo. Lipoprotein oxidation was measured in 3 distinct models of infection and inflammation. Syrian hamsters were injected with bacterial lipopolysaccharide (LPS), zymosan, or turpentine to mimic acute infection, acute systemic inflammation, and acute localized inflammation, respectively. Levels of oxidized fatty acids in serum and lipoprotein fractions were measured by determining levels of conjugated dienes, thiobarbituric acid–reactive substances, and lipid hydroperoxides. Our results demonstrate a significant increase in conjugated dienes and thiobarbituric acid–reactive substances in serum in all 3 models. Moreover, LPS and zymosan produced a 4-fold to 6-fold increase in conjugated diene and lipid hydroperoxide levels in LDL fraction. LPS also produced a 17-fold increase in LDL content of lysophosphatidylcholine that is formed during the oxidative modification of LDL. Finally, LDL isolated from animals treated with LPS was significantly more susceptible to ex vivo oxidation with copper than LDL isolated from saline-treated animals, and a 3-fold decrease occurred in the lag phase of oxidation. These results demonstrate that the host response to infection and inflammation increases oxidized lipids in serum and induces LDL oxidation in vivo. Increased LDL oxidation during infection and inflammation may promote atherogenesis and could be a mechanism for increased incidence of coronary artery disease in patients with chronic infections and inflammatory disorders.
Key Words: lipoproteins • atherosclerosis • infection • inflammation
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