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

Atherosclerosis. 1999 Jan;142(1):217-24. doi: 10.1016/s0021-9150(98)00207-x.

Abstract

We have previously shown that low-density (LDL) and high-density (HDL) lipoprotein from healthy subjects can promote in vitro prostaglandin (PG) release by murine macrophages. In this pilot study, we have measured PG production induced by lipoproteins of six diabetic patients with poor metabolic control, compared to five healthy controls. Plasma lipoprotein levels were similar in both groups. Lipoprotein fractions were purified by sequential ultracentrifugation. After lipoprotein incubation with cells, supernatants were extracted and PG quantified by HPLC. In presence of LDL, in control subjects, there was an increase in total PG production, mainly due to thromboxane B2 (TxB2). In diabetic patients, the secretion pattern was similar. In presence of HDL, in control subjects, total PG secretion was also increased, but 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 between TxB2 and prostacyclin. Comparison of means of areas under curve for the two groups studied showed that LDL increased all PG secretion in diabetic patients compared to controls (P < 0.05 for PGF2alpha), while HDL increased all PG secretion in controls compared to diabetic patients, except PGF2alpha. Our work suggests a key role of LDL in TxB2 secretion in diabetic patients, which is a major proaggregant and vasoconstrictive agent. There was also an increased secretion of all PG in diabetic patients.

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / metabolism*
  • Epoprostenol / metabolism
  • Female
  • Humans
  • Leukemia P388 / metabolism*
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, HDL / pharmacology*
  • Lipoproteins, LDL / metabolism
  • Lipoproteins, LDL / pharmacology*
  • Macrophages / metabolism*
  • Male
  • Mice
  • Prostaglandins / metabolism*
  • Thromboxane B2 / metabolism
  • Tumor Cells, Cultured

Substances

  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Prostaglandins
  • Thromboxane B2
  • Epoprostenol