Mechanisms involved in the differential reduction of omega-3 and omega-6 highly unsaturated fatty acids by structural heart disease resulting in 'HUFA deficiency'

摘要

The causes of reduced levels of omega-3 and omega-6 highly unsaturated fatty acids ("HUFA deficiency") inheart failure remain unresolved. HUFA profiles were examined in the serum of 331 patients with failing versus nonfailingheart disease. Arachidonic acid was positively correlated (P < 0.001) with eicosapentaenoic acid (EPA) (r = 0.40) and docosahexaenoicacid (DHA) (r = 0.53) and negatively with palmitic (r = 0.42), palmitoleic (r = 0.38), and oleic acid (r =0.48). Delta-5 desaturase activity was reduced (P < 0.01) in heart failure patients with low ejection fraction, dilatation, increasedwall stress, and reduced heart rate variability (SDNN). In these patients, the reduced (P < 0.01) HUFA and increasedpalmitic (P < 0.01) and oleic acid (P = 0.05) arose from separate influences involving reduced cardiac contractility(arachidonic acid and palmitic acid predicted by ejection fraction) and chamber dilatation (DHA and oleic acid predicted byend-diastolic diameter). A low DHA (0.2%-0.9% versus 1.4%-3.1%) was associated (P < 0.025) with atrial dilatation (44 ±8 mm versus 40 ± 8 mm). Equidirectional but less pronounced effects on HUFA were induced by sympathetic activationand (or) insulin resistance (fat and sugar fed to deoxycorticosterone acetate (DOCA)-salt rats) but not by compensated cardiacoverload alone (DOCA-salt or aortic constriction), or reduced fatty acid oxidation (CPT-1 inhibition). Based on administrationof omega-3 HUFA (OMACOR), dilatation is identified as a target for 1-2 g omega-3 HUFA·day-1. Interventionsfor reduced arachidonic acid remain to be explored.