Infection and inflammation induce LDL oxidation in vivo

Area of Science:

• Biochemistry
• Immunology
• Cardiovascular Research

Background:

• Epidemiological studies link chronic infections and inflammation to increased coronary artery disease (CAD).
• Oxidative modification of lipoproteins is a key factor in atherosclerosis development.

Purpose of the Study:

• To investigate if the host response to infection and inflammation induces lipoprotein oxidation in vivo.
• To test the hypothesis that inflammatory processes promote atherogenesis via lipoprotein oxidation.

Main Methods:

• Three models of acute inflammation were used in Syrian hamsters: bacterial lipopolysaccharide (LPS), zymosan, and turpentine.
• Serum and lipoprotein oxidation markers (conjugated dienes, TBARS, lipid hydroperoxides) were measured.
• Low-density lipoprotein (LDL) susceptibility to ex vivo oxidation was assessed.

Main Results:

• Significant increases in serum conjugated dienes and TBARS were observed in all models.
• LPS and zymosan treatments markedly elevated LDL conjugated dienes and lipid hydroperoxides.
• LPS increased lysophosphatidylcholine in LDL and enhanced its susceptibility to copper-induced oxidation.

Conclusions:

• The host response to infection and inflammation demonstrably increases oxidized lipids and induces LDL oxidation in vivo.
• Increased LDL oxidation during inflammatory states may contribute to atherogenesis.
• This mechanism could underlie the elevated CAD risk in patients with chronic infections and inflammatory disorders.