Abstract

Inflammation is associated with several cardiovascular diseases and mast cells have been implicated in many of these, but their precise role remains unclear. We hypothesize that tryptase, a pre formed mast cell mediator, stimulates rabbit ventricular myocyte calcium independent phospholipase A2 (iPLA2) activity, resulting in increased arachidonic acid and prostaglandin E2 (PGE2) release. Tryptase stimulation (20 ng/ml) increased iPLA2 activity after 5 mins (3.56 ± 0.12 to 5.87 ± 0.31 nmol/mg protein/min, n=6, p<0.01). This was accompanied by increased arachidonic acid (1.02 ± 0.12 to 5.02 ± 0.21%, n=6, p<0.01) and PGE2 release (4.50 ± 0.30 to 16.70 ± 0.59 ng/mg protein, n=8, p<0.01) in stimulated myocytes. To distinguish between different myocardial iPLA2 isoforms, we pretreated ventricular myocytes with the R‐ and S‐ enantiomers of bromoenol lactone (BEL, 5 μM, 10 mins) to selectively inhibit iPLA2γ and β respectively. (R)‐BEL pretreatment resulted in complete inhibition of tryptase‐stimulated iPLA2 activity, arachidonic acid and PGE2 release, suggesting the iPLA2γ is activated in response to tryptase. Pretreatment with (S)‐BEL had little effect on tryptase‐stimulated responses. Previous studies suggest that PGE2 may be cardioprotective. Thus tryptase release from activated mast cells may play a protective role in cardiac inflammation via iPLA2γ activation and increased PGE2 release from myocytes.

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