Variation in Human Erythrocyte Membrane Unsaturated Fatty Acids: Correlation With Cardiovascular Disease

Abstract

Whether cell membrane fatty acid (FA) composition is a useful indicator of vascular disease is unclear. To study variation of erythrocyte (RBC) membrane FA in samples from healthy volunteers, hospitalized patients, and cardiac troponin I-elevated patients with myocardial damage without a priori assumptions as to FA composition. We separated FAs extracted from RBCs by gas chromatography and identified them by mass spectrometry. Fatty acids with abundance greater than 1% of total were quantified and compared: hexadecanoic (C16:0), octadecadienoic (C18:2), cis- and trans-octadecenoic (C18:1), and eicosatetraenoic (C20:4) acids. Deuterated standards established proportionality of FA recovery. The cis- and trans-C18:1 identification was verified by comparison with standards. In troponin-positive samples, C18:2 to C18:1 ratios were increased 30% compared with healthy controls or with random patient samples. Erythrocyte trans-C18:1 had a wide variation, approximately 10-fold, in all groups but without differences between groups. Replicates showed that the wide range of RBC trans-FA load is not due to analytic variation. In healthy subjects, the RBC content of lower- molecular weight FAs (C16-C18) correlated with serum low-density lipoprotein cholesterol, but despite the established relationship between dietary trans-FA and increased low-density lipoprotein cholesterol, lipid profiles had no correlation with RBC trans-FA content. Erythrocyte accumulation of unsaturated FA may be a useful indicator of vascular disease, whereas the wide range in trans-FAs suggests that both diet and genetic variation affect RBC trans-FA accumulation. Unsaturated FAs increase membrane fluidity and may reflect a natural response to subclinical vascular changes, which may in turn reflect increased risk of clinical disease.