title: Mechanisms involved in the differential reduction of omega-3 and omega-6 highly unsaturated fatty acids by structural heart disease resulting in "HUFA deficiency".
abstract: The causes of reduced levels of omega-3 and omega-6 highly unsaturated fatty acids ("HUFA deficiency") 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 < 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 < 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 < 0.01) HUFA and increased palmitic (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 by end-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 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.
authors.affiliation: Experimental Cardiology Laboratory, Department of Internal Medicine - Cardiology, Philipps University Marburg, Baldingerstrasse 1, 35043 Marburg, Germany. rupp@staff.uni-marburg.de
authors.forename: Heinz
authors.initials: H
authors.lastname: Rupp
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Rupp
authors.forename: Peter
authors.initials: P
authors.lastname: Alter
authors.forename: Bernhard
authors.initials: B
authors.lastname: Maisch
mesh_terms: D000818:Animals; D000090943:Delta-5 Fatty Acid Desaturase; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000097:blood; D005227:Fatty Acids / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000097:blood* / Q000494:pharmacology; D043371:Fatty Acids, Omega-6 / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000178:diet therapy* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D004338:Drug Combinations; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D004281:Docosahexaenoic Acids; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D015118:Eicosapentaenoic Acid; C405603:Omacor; D044943:Fatty Acid Desaturases