Presence of paraoxonase in human interstitial fluid

Human serum paraoxonase (PON1) is postulated to have anti-atherosclerotic properties through its ability to prevent lipid peroxide generation on LDL. However, in order to perform this role it must be present in interstitial fluid, to prevent LDL oxidation which takes place in the sub-intimal space of the artery wall. The PON1 activity in interstitial fluid was 15.7 (2.3-183.0) (median (range)) nmol/min/ml compared to 105.3 (74.6-323.9) nmol/min/ml in serum. The PON1 concentration in interstitial fluid was found to be 20.2 (1.1-78.1) microg/ml (median (range)) compared to 109.6 (11.1-485.7) microg/ml in serum. Interstitial fluid PON1 concentration was dependent on the interstitial fluid apo AI concentration (r = 0.690, P < 0.005) indicating PON1 remained associated with HDL. However, the ratio of PON1 concentration to apo AI was lower in interstitial fluid (0.60 +/- 0.20) than in the serum (0.95 +/- 0.18) (P < 0.001) indicating sequestration of PON1 in the sub-intimal space. Therefore, PON1 is present and active in interstitial fluid where it can perform its anti-atherosclerotic function.