Background: Translocation and activation of protein kinase C (PKC) has been shown to occur in the ischemic heart. It is, however, controversial if this activation process occurs also in the non-ischemic, remote area of an infarcted heart early after infarction. Furthermore, the mechanisms contributing to the translocation process induced by acute myocardial ischemia in both areas are not fully elucidated.
Methods: Regional myocardial infarction was induced by left anterior descending coronary artery (LAD-) ligation in situ for 2.5 min in rats or in pigs. To evaluate the influence of angiotensin and bradykinin signaling, ramiprilat, candesartan, or the bradykinin-receptor antagonist HOE 140 was given. In biopsies from the ischemic and the non-ischemic remote area, PKC activity and intracellular isozyme distribution were determined.
Results: Translocation and activation of PKC could be demonstrated for the first time in the myocardium remote from the infarcted area. This activation was conserved both in pigs and in rats. All major cardiac isozymes of PKC were involved. Whereas bradykinin-receptor blockade had no effect, both angiotensin-converting enzyme inhibition (ACEI) and angiotensin receptor could effectively block this activation process of PKC.
Conclusion: In the area remote from a myocardial infarction, the activation of PKC could be detected for the first time as early as 2.5 min after LAD ligation. This newly characterized activation in the non-infarcted area can be prevented by ACEI via an angiotensin-AT1-receptor-dependent mechanism. It is supposed that this newly characterized activation process of PKC plays an important role in the signal transduction in the remote myocardium in acute myocardial infarction as a trigger for the late development of hypertrophy and heart failure.