In vitro stimulation of HDL anti-inflammatory activity and inhibition of LDL pro-inflammatory activity in the plasma of patients with end-stage renal disease by an apoA-1 mimetic peptide

Features of end-stage renal disease such as oxidative stress, inflammation, hypertension, and dyslipidemia are associated with accelerated atherosclerosis and increased risk of death from cardiovascular disease. By inhibiting the formation and increasing the disposal of oxidized lipids, HDL exerts potent antioxidant and anti-inflammatory actions. Given that apolipoproteinA-1 can limit atherosclerosis, we hypothesized that an apolipoproteinA-1 mimetic peptide, 4F, may reduce the proinflammatory properties of LDL and enhance the anti-inflammatory properties of HDL in uremic plasma. To test this, plasma from each of 12 stable hemodialysis patients and age-matched control subjects was incubated with 4F or vehicle. The isolated HDL and LDL fractions were added to cultured human aortic endothelial cells to quantify monocyte chemotactic activity, thus measuring their pro- or anti-inflammatory index. The LDL from the hemodialysis patients was more pro- inflammatory and their HDL was less anti-inflammatory than those of the control subjects. Pre-incubation of the plasma from the hemodialysis patients with 4F decreased LDL pro- inflammatory activity and enhanced HDL anti-inflammatory activity. Whether 4F or other apolipoproteinA-1 mimetic peptides will have any therapeutic benefit in end-stage renal disease will have to be examined directly in clinical studies.