Secretory non-pancreatic phospholipase A₂: Influence on lipoprotein metabolism

Lipoprotein metabolism is markedly altered during inflammation. The concentration of human secretory phospholipase A₂ (sPLA₂) can increase hundreds of fold in inflammatory fluids and in the circulation. It was detected in atherosclerotic lesions where many inflammatory genes are induced. As sPLA₂ has been reported to act on lipoproteins as substrates, lipoprotein profiles in transgenic mice expressing sPLA₂ were studied. HDL levels were markedly decreased in transgenic mice overexpressing sPLA₂. HDL in the transgenics were smaller in size, with a significant decrease (11%) in phospholipid content compared to nontransgenic littermates. In sPLA₂ transgenic mice and transgenic mice expressing both sPLA₂ and human apolipoprotein B (apoB), the concentrations of apoB-containing lipoproteins were not altered. We conclude that sPLA₂ alters HDL metabolism and could be responsible for the depressed levels of HDL that exist during chronic inflammatory diseases.