Influence of Trimetazidine on the synthesis of complex lipids in the heartand other target organs

Trimetazidine exerts antianginal properties at the cellular level, without haemodynamic effect in clinical and experimental conditions. This cytoprote ction was attributed to a decreased utilization of fatty acids for energy p roduction, balanced by an increased incorporation in structural lipids. Thi s study evaluated the influence of Trimetazidine on complex lipid synthesis from [2-H-3] glycerol, in ventricular myocytes, isolated rat hearts and in vivo in the myocardium and several other tissues. In cardiomyocytes, Trime tazidine increased the synthesis of phosphatidylcholine (+ 80%), phosphatid yl-ethanolamine (+ 210%), phosphatidyl-inositol (+ 250%) and cardiolipid ( 100%). The common precursor diacylglycerol was also increased (+ 40%) wher eas triacylglycerol was decreased (-70%). Similar results were obtained in isolated hearts with 10 muM Trimetazidine (phosphatidyl-choline + 60%, phos phatidyl-ethanolamine + 60%, phosphatidyl-inositol + 100% and cardiolipid 50%), the last two phospholipids containing 85% of the radioactivity. At 1 muM, Trimetazidine still stimulated the phospholipid synthesis although th e difference was found significant only in phosphatidyl-inositol and cardio lipid. In vivo studies (10 mg/kg per day for 7 days and 5 mg/kg, i.p. befor e the experiment) revealed significant changes in the intracellular lipid b iosynthesis, with increased labelling of phospholipids and reduced incorpor ation of glycerol in nonphosphorous lipids. Trimetazidine increased the gly cerol uptake from plasma to the other tissues (liver, cochlea, retina), res ulting in an altered lipid synthesis. The anti-anginal properties of Trimet azidine involve a reorganisation of the glycerol-based lipid synthesis bala nce in cardiomyocytes, associated with an increased uptake of plasma glycer ol that may contribute to explain the pharmacological properties reported i n other organs.