Serum Paraoxonase After Myocardial Infarction

Abstract

Abstract-HDL has been shown to prevent the oxidative modification of LDL. The antioxidant activity of HDL is believed to reside in its enzymes, particularly paraoxonase. Human serum paraoxonase (PON1) is closely associated with a specific HDL subfraction also containing apoA1 and clusterin. Recently PON1 has been implicated in the pathogenesis of atherosclerosis. We have examined the activity, concentration, and specific activity of PON1 in 50 patients on admission to hospital immediately after acute myocardial infarction (MI) and in 48 age-and gender-matched controls. Serum PON1 activity and concentration were significantly lower in patients with MI than in controls (activity, 221. ⅐ mL Ϫ1 at day 42 but was still significantly less than that of controls. No significant variation in PON1 concentration occured in the days after MI or at 6 weeks. Also, no significant variation in specific activity was seen after MI. When the patients were divided into subgroups based on whether or not they received thrombolytic therapy on admission to hospital, no significant difference in PON1 levels was observed. Serum HDL cholesterol in patients with MI on admission was not significantly different than in controls, and the decrease that occurred by the fifth day after MI did not explain the lower PON1 levels. We conclude that low serum PON1 activity in patients with MI may be a consequence of the coronary event itself or could have been present before MI. The low PON1 activity was also not explicable on the basis of PON1 genotypes because the prevalence of genotypes associated with low activity was not sufficient to explain fully the difference in activity levels between patients and controls. The explanation for the low PON1 activity was most likely a decrease in serum PON1 concentration. The importance of PON1 as a predictive risk factor for MI should be assessed in future studies.

Decreased HDL-Dependent Paraoxonase and Arylesterase Enzyme Activity May Indicate a Worse Prognosis in Multiple Myeloma

“…Human serum PON1 indicates neither age-related change in activity nor gender differences (Geldmacher et al, 1983). Reduced PON1 enzyme activities have been showed in several groups of patients with hypercholesterolemia, diabetes mellitus, renal failure and cardiovascular disease, in which the patients are under increased oxidative stress (Mackness et al, 1991;Ayub et al, 1999;Yılmaz et al, 2012).…”

Increased methionine sulfoxide content of apoA-I in type 1 diabetes

“…At least two HDL-bound proteins are involved with LPO detoxification, paraoxonase (PON-1) (18,19) and apolipoprotein A-I (apoA-I) (20). PON-1 is a lactonase that protects against LDL and HDL oxidation by hydrolyzing oxidized fatty acids to lactones; plasma or serum PON-1 concentration or activity is inversely correlated with CVD and is commonly decreased in diabetes and in renal disease (21)(22)(23)(24). ApoA-I, the major protein of HDL, is involved with the mobilization of cholesterol from oxidized LDL and macrophages of the arterial wall during reverse cholesterol transport (25) and also reduces LPOs, using methionine (Met) residues as the reductant and producing methionine sulfoxide [Met(O)] (see below).…”

Acute myocardial infarction is associated with increased susceptibility of serum lipids to copper‐induced peroxidation in vitro

“…One possibility is that HDL-associated proteins are involved. Specifically, acute phase response results in a decrease in both the level and activity of the antioxidative enzyme paraoxonase (as shown after MI) 22 and increased level of the potentially pro-oxidative copper-chelator ceruloplasmin (as shown after cardiac surgery). 23 These changes may explain our results as well as those of previous studies showing that HDL taken from patients during the acute phase, unlike under normal conditions, did not protect LDL against oxidation induced by cocultures of artery wall cells.…”