Abstract 3943: Prevention of Left Ventricular Remodeleing and Dysfunction in Pressure Overload by Omega-3 Fatty Acid Supplementation is Associated With Alteration in the Cardiac Lipidome, Not Changes in Gene Transcription
Dietary supplementation with omega-3 fatty acids (FA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevents hypertension-induced heart failure. The mechanism responsible for this effect is unclear, but could be due to changes in
cardiac phospholipid composition, or
We investigated these two possibilities in rats fed either 2.3% EPA+DHA or normal chow (NC) (both 15% fat) and subjected to aortic banding (AAB) for 12 wks. EPA+DHA preserved LV function vs. NC, as seen in maintenance of end diastolic volume (0.49±0.02 vs 0.69±0.04 mL) and systolic volume (0.06±0.01 vs 0.13±0.01 mL) (p<0.001). LV membrane phospholipid composition was also dramatically modified by EPA+DHA. EPA and DHA in membrane phospholipids increased from 11.8% of total FA with NC to 27.7% with EPA+DHA (p<0.001), and arachidonic acid (a precursor of inflammatory eicosanoids) decreased from 23.6% with NC to 9.2% (p<0.001). EPA+DHA decreased inflammatory markers (plasma TNFα and urine thromboxane B2). Plasma TNFα increased with AAB in NC (14.4 to 35.5pg/ml; p=0.004), but was undetectable in sham rats fed EPA+DHA, and was reduced to 3.6 pg/ml in AAB (p<0.001 vs. NC AAB). Effects of EPA+DHA on gene transcription assessed by microarray: AAB significantly altered 677 and 397 genes in the NC and EPA+DHA diets, respectively, but EPA+DHA increased transcripts for only 67 and 82 genes compare to NC in sham and AAB groups, respectively. Targeted analysis with RT-PCR found no changes in PPARα-regulated genes (MCAD, PDK4,UCP3, etc). Effects of individual long chain FA on activation of the expression of PPARα-regulated genes were evaluated in isolated adult rat cardiomyocytes incubated with EPA, DHA, EPA+DHA, α-linolenic acid or oleate. There were no differences in the induction of PPARα-regulated genes among these FAs. Taken together, these results indicate that the beneficial effects of EPA+DHA are not mediated by alternations in gene expression, but rather through major changes in the cardiac lipidome. Specifically, the fall in arachidonic acid in cardiac phospholipids was associated with a fall in inflammatory markers and prevention of LV remodeling.