Lysophosphatidylcholine accumulation in cardiomyocytes requires thrombin activation of Ca2+-independent PLA2

Lvsonhosoha-tidylcholine (LPG) accumulates during ischemia or following thrombin stimulation of cardiac myocytes. We determined whether LPC accumulation reflects increased LPC production via phospholipase A₂ (PLA₂) activation, inhibition of LPC catabolism, or a combination of both. Thrombin-stimulated normoxic myocytes demonstrated a 1.5-fold increase in LPC content and a 2- to 2.5-fold increase in membrane-associated, Ca²⁺-independent PLA₂ activity. Despite PLA₂ activation, hypoxia alone did not increase LPC content. Thrombin-stimulated hypoxic myocytes demonstrated a 2.5-fold increase in LPC content with no further increase in PLA₂ activity. Inhibition of Ca²⁺-independent PLA₂ prevented the thrombin-induced increase in both PLA2 activity and LPC content under normoxic and hypoxic conditions. Pharmacological blockade of the hypoxia-induced inhibition of LPC catabolism did not affect hypoxia or thrombin-induced PLA2 activation or normoxic, thrombin-induced LPC accumulation but greatly diminished the magnitude of LPC accumulation after thrombin stimulation of hypoxic myocytes. Thus accumulation of LPC during ischemia or after thrombin stimulation is absolutely dependent on PLA2 activation and further augmented by inhibition of LPC catabolism.