Mechanisms involved in the differential reduction of omega-3 and omega-6 highly unsaturated fatty acids by structural heart disease resulting in %26quot;HUFA deficiency%26quot;

作者：Rupp Heinz^*; Rupp Thomas P; Alter Peter; Maisch Bernhard

来源：Canadian Journal of Physiology and Pharmacology, 2012, 90(1): 55-73.

DOI：10.1139/Y11-101

• cardiac dilatation
• hypertrophy
• fatty acids
• highly unsaturated fatty acids
• heart failure
• DOCA-salt hypertension
• aortic constriction
• fenofibrate
• etomoxir
• omega-3-acid ethyl esters

The causes of reduced levels of omega-3 and omega-6 highly unsaturated fatty acids (%26quot;HUFA deficiency%26quot;) in heart failure remain unresolved. HUFA profiles were examined in the serum of 331 patients with failing versus nonfailing heart disease. Arachidonic acid was positively correlated (P %26lt; 0.001) with eicosapentaenoic acid (EPA) (r = 0.40) and docosahexaenoic acid (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 %26lt; 0.01) in heart failure patients with low ejection fraction, dilatation, increased wall stress, and reduced heart rate variability (SDNN). In these patients, the reduced (P %26lt; 0.01) HUFA and increased palmitic (P %26lt; 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 by end-diastolic diameter). A low DHA (0.2%-0.9% versus 1.4%-3.1%) was associated (P %26lt; 0.025) with atrial dilatation (44 +/- 8 mm versus 40 +/- 8 mm). Equidirectional but less pronounced effects on HUFA were induced by sympathetic activation and (or) insulin resistance (fat and sugar fed to deoxycorticosterone acetate (DOCA)-salt rats) but not by compensated cardiac overload alone (DOCA-salt or aortic constriction), or reduced fatty acid oxidation (CPT-1 inhibition). Based on administration of omega-3 HUFA (OMACOR), dilatation is identified as a target for 1-2 g omega-3 HUFA.day(-1). Interventions for reduced arachidonic acid remain to be explored.

• 出版日期2012-1