Background/Purpose:   Oxidation products of arachidonic acid and linoleic acid including hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs), respectively, play an important role in the pathogenesis of atherosclerosis and have been associated with endothelial cell activation.  HETEs and HODEs contribute to the oxidation of low density lipoprotein (LDL) and their accumulation in high density lipoprotein (HDL) impairs HDL function, which increases risk of vascular damage.  The current work evaluated the levels of HETEs and HODEs in HDL isolated from patients with dermatomyositis (DM) and polymyositis (PM) since vascular damage is implicated in the pathogenesis of both muscle and lung disease in DM/PM patients,

Methods: HDL was isolated by ultracentrifugation from plasma of 12 DM patients, 12 PM patients and 12 healthy controls. 5-HETE, 12-HETE, 15-HETE, 9-HODE, and 13-HODE levels in HDL were measured by mass spectrometry as described previously (Imaizumi et al. Drug Metab Lett. 2010; 4(3): 139-48). HDL’s anti-inflammatory function was measured by a cell free assay as described previously (Charles-Schoeman et al. Arthritis Rheum. 2009; 60(10): 2870-9). Lipoprotein cholesterol levels were determined by standard methods.

Results: 5-HETE, 15-HETE, 9-HODE and 13-HODE levels were significantly increased in HDL from patients with PM compared to healthy controls (see Table).  5-HETE was also significantly increased in HDL from DM patients compared to controls and was significantly correlated with the HDL inflammatory index (r = 0.41, p=0.01); higher HDL-associated 5-HETE was associated with worse anti-oxidant capacity of HDL.  Myositis patients with interstitial lung disease (ILD) (n=14) had higher 13-HODE, 12-HETE, and 5-HETE levels in HDL compared to myositis patients without ILD (n=10) (p values= 0.05, 0.06, and 0.13 respectively). Patients with moderate to severe ILD suggested by the diffusing capacity of the lungs for carbon monoxide (DLCO) <50% of predicted also showed trends for higher HDL-associated 5-HETE, 12-HETE, and 13-HODE levels compared to ILD patients with less severe disease (DLCO >50%) (see Table). 5-HETE and 12-HETE levels were inversely correlated with DLCO, r = -0.58 (p=0.02) and r = -0.49 (p=0.05), respectively. 

Conclusion:   Oxidation products of arachidonic acid and linoleic acid are increased in HDL from patients with PM and DM compared to healthy controls.  Increased 5-HETE in HDL was associated with impaired HDL anti-oxidant function and was inversely associated with DLCO in patients with myositis. Our results suggest that therapeutic agents such as apoA-I mimetic peptides, which bind oxidized fatty acids and reduce vascular damage and lung injury in animal models, may warrant further investigation in DM/PM patients.

All values mean ± standard deviation.  *p value ≤ 0.05 compared to controls.

Note: Recent DLCO value not available for one patient with known ILD.