Eicosanoid precursors: potential factors for atherogenesis in diabetic CAPD patients?

Abstract

Prostaglandins, thromboxanes, and other eicosanoids represent a widespread lipid-mediator system for intercellular signalling, and, hence, have multiple cellular actions. Thus it is not surprising that numerous events in the pathogenesis of atherosclerosis are associated with an altered formation of eicosanoids. To reconsider the availability of eiconsanoid precursors as one possible cause of atherogenesis, the dietary intake and the serum concentrations of arachidonic acid (AA) and eicosapentaenoic acid (EPA) were determined in patients with high risk for atherosclerosis on continuous ambulatory peritoneal dialysis (CAPD) with and without diabetes in comparison to healthy controls and diabetic patients without late complications. The factor AA/EPA in serum was created as a marker for the atherosclerosis risk. The setting was in a CAPD unit in one city hospital. There were 26 CAPD patients [9 with insulin-dependent diabetes mellitus (IDDM), 9 with noninsulin-dependent diabetes mellitus (NIDDM), and 8 without diabetes], 27 IDDM without late complications, and 41 healthy control persons. The AA levels in serum were significantly higher in all of the CAPD groups. In contrast, the EPA concentrations in serum were significantly lower in the CAPD groups, with the lowest EPA levels found in the CAPD-IDDM group. Therefore, the factors AA/EPA in serum were significantly higher in all of the CAPD groups, and again significantly higher in the CAPD-IDDM group than in the other CAPD groups. No differences in the amount of dietary intake of AA existed between the groups. The daily intake of EPA was significantly highest in the control group. Higher concentrations of AA and a lack of n-3 fatty acids lead in the presence of a reduced prostaglandin I2 biosynthesis, to a higher formation rate of potentially proatherogenic metabolites such as thromboxane A2, a vasoconstricting and platelet aggregating agent. Thus, the quotient AA/EPA could possibly be used as a marker of atherogenicity in the future.