Effects of low density and high density lipoproteins isolated from non-insulin dependent diabetic patients on prostaglandin secretion by mouse macrophage cell line P388D1

We have previously shown that low-density (LDL) and high-density (HDL) lipo protein from healthy subjects can promote in vitro prostaglandin (PG) relea se by murine macrophages. In this pilot study, we have measured PG producti on induced by lipoproteins of six diabetic patients with poor metabolic con trol, compared to five healthy controls. Plasma lipoprotein levels were sim ilar in both groups. Lipoprotein fractions were purified by sequential ultr acentrifugation. After lipoprotein incubation with cells, supernatants were extracted and PG quantified by HPLC. In presence of LDL, in control subjec ts, there was an increase in total PG production, mainly due to thromboxane B2 (TxB2). In diabetic patients, the secretion pattern was similar. In pre sence of HDL, in control subjects, total PG secretion was also increased, b ut it was balanced between TxB2 and prostacyclin. In diabetic patients, at low HDL concentration (10 mg/l) the secretion was mainly due to TxB2, while at higher HDL concentrations (100 mg/l), the secretion was balanced betwee n TxB2 and prostacyclin. Comparison of means of areas under curve for the t wo groups studied showed that LDL increased all PG secretion in diabetic pa tients compared to controls (P < 0.05 for PGF2 alpha), while HDL increased all PG secretion in controls compared to diabetic patients, except PGF2 alp ha. Our work suggests a key role of LDL in TxB2 secretion in diabetic patie nts, which is a major proaggregant and vasoconstrictive agent. There was al so an increased secretion of all PG in diabetic patients. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.