HDL Function and Metabolism During Inflammation PPG Project 1

Frederick C. de Beer, M.D.
Project Director

Sean Davidson
Co-Investigator

Bela Asztalos
Co-Investigator

Intimate associations exist between atherosclerosis and inflammation.  The atherosclerotic process itself has features of chronic inflammation.  Furthermore, the process of atherosclerosis is profoundly accelerated by chronic inflammatory disease states such as rheumatoid arthritis.  Recently higher rates of first and subsequent myocardial infarctions, as well as strokes, were observed in patients with acute urinary and respiratory infections.  Perhaps most notable amongst the plethora of metabolic changes that affect lipid and lipoproteins during inflammation are the structural and metabolic alterations of HDL.  In practically all species there is a significant decrease of HDL cholesterol and apolipoprotein A-I (apoA-I).  Serum amyloid A protein (SAA) is dramatically induced by cytokines and can even become the major apolipoprotein of HDL. The same cytokines concomitantly induce the inflammatory phospholipases particularly group IIA secretory phospholipase A2 (group IIA sPLA2) that hydrolyze HDL surface phospholipids with significant metabolic sequelae.  In the short term these changes are likely required for survival, but if chronically maintained could have long-term pathological consequences.