Infection and inflammation induce LDL oxidation in vivo

Epidemiological studies have shown an increased incidence of coronary arter y disease in patients with chronic infections and inflammatory disorders. B ecause oxidative modification of lipoproteins plays a major role in atheros clerosis, the present study was designed to test the hypothesis that the ho st 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 lipopolysacc haride (LPS), zymosan, or turpentine to mimic acute infection, acute system ic inflammation, and acute localized inflammation, respectively. Levels of oxidized fatty acids in serum and lipoprotein fractions were measured by de termining levels of conjugated dienes, thiobarbituric acid-reactive substan ces, and lipid hydroperoxides, Our results demonstrate a significant increa se in conjugated dienes and thiobarbituric acid-reactive substances in seru m in all 3 models. Moreover, LPS and zymosan produced a 4-fold to 6-fold in crease in conjugated diene and lipid hydroperoxide levels in LDL fraction. LPS also produced a 17-fold increase in LDL content of lysophosphatidylchol ine that is formed during the oxidative modification of LDL, Finally, LDL i solated from animals treated with LPS was significantly more susceptible to ex vivo oxidation with copper than LDL isolated from saline-treated animal s, and a 3-fold decrease occurred in the lag phase of oxidation. These resu lts demonstrate that the host response to infection and inflammation increa ses oxidized lipids in serum and induces LDL oxidation in vivo. Increased L DL oxidation during infection and inflammation may promote atherogenesis an d could be a mechanism for increased incidence of coronary artery disease i n patients with chronic infections and inflammatory disorders.