Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis.

OBJECTIVE: To evaluate the impact of chronic inflammation on lipoprotein lipase (LPL) levels and tri-glyceride metabolism in patients wit rheumatoid arthritis (RA).
DESIGN: Plasma levels of LPL activity and mass before and after heparin were determined in post-menopausal women with active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with triglyceride levels were also measured before and 6 h after an oral fat load.
SETTING: The study was performed on in- and outpatients at a University Rheumatology clinic. The controls came from the same reference area.
SUBJECTS: Altogether 17 consecutive postmenopausal female patients with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the fat load. Of these, one patient and one control were excluded. MAIN OUTCOME MEASURES: LPL determination: basal levels and post-heparin levels of LPL activity and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides), lipoprotein levels (high density lipoprotein, HDL: low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor alpha. TNF-alpha: interleukin 1 beta, IL-1 beta: and interleukin-6. IL-6). Fat tolerance test: LPL activity. mass and triglyceride levels before and 6 h after a per oral fat load.
RESULTS: Pre-heparin LPL mass (P < 0.01) and activity (P < 0.01) were significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters: it was significant for orosomucoid (rs = -0.63, P < 0.05) and C-reactive protein (CRP) (rs = -0.54, P < 0.05) and close to significant for haptoglobin (rs = -0.48, P = 0.087) and IL-6 (rs = -0.52, P = 0.061). Six hours after.a lipid load the LPL activity and mass were significantly lower in RA (P < 0.05 and P < 0.01, respectively) but the triglyceride level was not significantly different compared to controls.
CONCLUSION: An inverse relationship exists between inflammatory status and pre-heparin LPL mass. Preheparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor-related protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of the level of monomeric LPL in plasma may thus be beneficial for remnant catabolism. The same mechanism may on the other hand increase macrophage uptake of lipids. This may not affect global lipid metabolism but may be important in driving the atherosclerotic process in the vessel wall.