Figure 1.

Protective role of paraoxonase 1 in cardiovascular disease and inflammation. Ischemic stroke is a very prevalent complication of atherosclerosis. PON1 may have a protective role in this disorder as it carries both antioxidant and anti-inflammatory functional properties. In this diagram we summarize the current knowledge on the main functional activities of PON1 a protective factor vis-a-vis atherogenesis. Reactive oxygen species issued from inflammation oxidize lipids in LDL (1) or cell membranes (2) producing oxidized phospholipids (3). PON1 produced in the liver and carried by HDL (4) exerts a lactonizing and lactonase activity (5) that results in the production of a carboxylic acid (5), eliminating further damage. The lactonase activity of PON1 also permits it to detoxify homocysteine thiolactone (6). This compound is associated with increased cardiovascular risk, since homocysteinylation of proteins (coagulation factors, lipoproteins, endothelial receptors) is atherogenic (7). Homocysteine thiolactone is one of the natural substrates of PON1, which hydrolyzes it to innocuous homocysteine (8). PON1 also exerts its salutatory action on macrophages and other inflammatory cells (9), preventing cellular oxidative stress and blocking cytokine cascades that aggravate inflammation that may lead to enhanced atherogenesis and neurovascular disease (10).