Significance of platelet‐activating factor acetylhydrolase in patients with non‐insulin‐dependent (type 2) diabetes mellitus

Abstract

Background: Non‐insulin dependent diabetes mellitus (NIDDM) represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continnous low‐grade inflammation and endothelial activation state. Plasma platelet ‐ activating factor ‐ acetylhydrolases (PAF‐AHs) are a subgroup of Ca2+ ‐independent phospholipase A2 family (also known as lipoprotein‐associated phospholipases A2) that hydrolyze and inactivate the lipid mediator platelet‐activating factor (PAF) and/or oxidized phospholipids. This enzyme is considered to play an important role in inflammatory diseases and atherosclerosis. The present study aims to investigate the relations between the levels of PAF‐AH activity and LDL‐cholesterol/HDL‐cholesterol (LDL‐ch/HDL‐ch) ratio in NIDDM patients as compared to controls. Methods: serum PAF‐AH activity was measured in 50 patients with dyslipidemia, in 50 NIDDM patients and in 50 controls (normal lipid and glucose levels). Total cholesterol, LDL‐ch, HDL‐ch, triglyceride and blood glucose were determined in all subjects. Results: All NIDDM patients display hiperlipidemia, with increased LDL‐ch and triglyceride levels. There is a significant correlation between LDL‐ch levels (especially LDL‐ch / HDL‐ch ratio) and PAF‐AH activity in dyslipidemic and NIDDM patients. Conclusion: Diabetic and dyslipidemic patients have an increased plasma PAF‐AH activity correlated with their LDL‐ch levels and mainly with LDL‐ch / HDL‐ch ratio. Plasma PAF‐AH high levels appear to be important as a risk marker for endothelial dysfunction in patients with NIDDM.

Electronegative low‐density lipoprotein subfraction from type 2 diabetic subjects is proatherogenic and unrelated to glycemic control

“…Increased PAF-AH activity associated with LDL(−), the fact that the expression of this enzyme is upregulated in inflammatory states [43] and that atherosclerosis is basically an inflammatory disease [44] support the notion that LDL(−) could rise in plasma in response to increased inflammation. In agreement therewith, low-grade inflammation in plasma from diabetic subjects is increased and PAF-AH activity is also enhanced in these patients [45,46]. Moreover, statin therapy, which is known to exert some antiinflammatory actions beyond its primary hypolipemic effect [47], decreased the proportion of LDL(−) in FH patients [9,10].…”

The inflammatory properties of electronegative low-density lipoprotein from type 1 diabetic patients are related to increased platelet-activating factor acetylhydrolase activity

“…It is generally accepted that atherosclerosis is accompanied by low-grade inflammation [35]. In this context, the current finding that increased PAF-AH in LDL(−) decreases after glycaemic optimisation and the observation that PAF-AH activity is increased in diabetic patients [36,37] points to underlying inflammation as a key factor in the generation of LDL(−) in diabetes. PAF-AH expression increases in response to inflammatory stimuli and hyperglycaemia and insulin resistance are associated with low-grade systemic inflammation.…”

Platelet-Activating Factor Acetylhydrolase Concentration in Children With Abdominal Obesity

“…8 Adults with non-insulin-dependent diabetes mellitus also have increased plasma PAF-AH activity, which is correlated with their LDLC level. 9 In our study, plasma PAF-AH concentration was correlated with LDLC level and waist/height ratio. Waist circumference is a major component of metabolic syndrome.…”