Background: Omega3 fatty acids (n3 PUFA) supplementation has been reported to reduce incidence of sudden cardiac death (SCD) in clinical trials (GISSI Prevenzione and GISSI HF) but the mechanism of such benefit is unclear. SCD during acute coronary ischemia and in heart failure is attributed to cellular calcium overload and consequent diastolic calcium release. We hypothesized that n-3 PUFA may reduce SCD by altering expression levels of calcium handling proteins.
Objective: To evaluate the effect of supplementation of n-3PUFA on the expression levels of calcium handing proteins in patients undergoing coronary artery bypass graft (CABG) surgery.
Methods: Patients undergoing CABG surgery received supplements of n-3 PUFA (Omacor, 2g/day)or a matched placebo (as part of clinical trial) prior to surgery and right atrial tissue obtained during CABG. Tissue samples divided into 4 parts and used for quantitative polymerase chain reaction, immuno-histochemistry and Western blot for calcium handling proteins and estimation of tissue n3 PUFA using gas chromatography.
Results: Supplementation of n-3 PUFA reliably increased tissue levels in human heart. Expression of ryanodine receptor was increased and that of phospholamban reduced in the n-3 PUFA treated group. Other calcium handling proteins were not significantly altered
Conclusion: n-3PUFA supplementation and incorporation in human cardiomyocyte membrane alters expression levels of calcium handling proteins ryanodine receptor and phospholamban which might reduce cellular calcium overload and prevent arrhythmogenic diastolic calcium release.
Expression of Calcium Handling Proteins | qPCR (n=30 in each group) | | | Immunofluorescence (n=8 in each group) | | | Western blot (n=8 in each group) | | |
| n-3 PUFA | Placebo | p | n-3 PUFA | Placebo | p | n-3 PUFA | Placebo | p |
| NCX | 0.26±0.07 | 0.17±0.05 | 0.09 | 68.2±4.4 | 55.9±4.17 | 0.07 | 1.05±0.14 | 1.01±0.10 | 0.85 |
| SERCA | 0.20±0.05 | 0.22±0.07 | 0.83 | 81.3±3.6 | 77.5±3.9 | 0.50 | 1.13±0.11 | 1.20±0.09 | 0.60 |
| RYR2 | 0.27±0.06 | 0.11±0.02 | 0.04 | 80.6±4.5 | 59.5±2.6 | 0.002 | 0.93±0.24 | 0.57±0.12 | 0.03 |
| PLB | 0.10±0.02 | 0.20±0.04 | 0.02 | 85.9±3.3 | 70.7±3.1 | 0.01 | 0.70±0.06 | 0.91±0.07 | 0.04 |
