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.

Dynamics of the Polyunsaturated Fatty Acids Values in the Blood of Chronic Heart Failure Patients

“…Омега-3 индекс эритроцитов периферической крови, отражающий содержание омега-3 ПНЖК в кардио-миоцитах, рассматривается как фактор прогноза сер-дечно-сосудистых событий [5,6]. Исследованиями последних лет установлено, что прогностическое зна-чение имеет не только содержание в крови омега-3, но и омега-6 ПНЖК [4,[7][8][9]. Вопросы изучения дина-мики ПНЖК при декомпенсации ХСН, а также на фоне ее лечения, остаются мало освещенными.…”

Mechanisms increasing n-3 highly unsaturated fatty acids in the heart

“…A high availability of fatty acids in an obese state is associated with increased fatty acid utilisation. However, in view of the finding that an increased fatty acid oxidation arising from fenofibrate treatment of young rats increased 20:4n-6 but not 22:6n-3 (Rupp et al 2012), involvement of other parameters has to be inferred. Because it is well documented that increased abdominal fat is associated with a raised sympathetic activity (Canale et al 2013;Rupp and Maisch 2003) and it was previously shown that a hypercaloric intake was associated with an increased heart rate (Rupp and Maisch 1999), it was examined Standardized ␤-coefficients were given for significant differences.…”

“…For safety reasons, hydrogen was used as carrier gas produced by an H2-50XR Hydrogen Generator (SRI Instruments, Torrance, California, USA). Extraction of triacylglycerols and phospholipids and fatty acid transesterification to methyl esters were done as previously described (Rupp et al 2006(Rupp et al , 2012 (Michaud et al 2002) was performed. As internal standard, C17:0 methyl heptadecanoate was used (Dr. Ehrenstorfer GmbH, Augsburg, Germany).…”

“…Precursors 24:6n-3 and 24:5n-6 are known to be produced in the endoplasmic reticulum and move to peroxisomes for removal of 2 carbons (Sprecher 1999). When rats were treated with etomoxir, inhibiting the fatty acid oxidation, 22:6n-3 was reduced in the ventricle, while 20:5n-3 remained unchanged (Rupp et al 2012). Because etomoxir exhibits an enclosing inhibitory action, not only on the mitochondrial CPT-1, but also on the peroxisomal carnitine octanoyltransferase, facilitating the transport of fatty acids through the peroxisomal membrane (Skorin et al 1992), it can be used to explore consequences of a selectively reduced production of 22:6n-3.…”

“…Progression of heart failure was associated with reduced omega-3 and omega-6 HUFA serum concentrations (Rupp et al 2009(Rupp et al , 2010(Rupp et al , 2012. In particular, it was recently shown that increased ventricular wall stress and a reduced left ventricular ejection fraction (LVEF) is associated with decreased DHA (22:6n-3) .…”