Abstract 3936: Temocapril Treatment Ameliorates Autoimmune Myocarditis Associated With Enhanced Cardiomyocyte Thioredoxin Expression
Background and Purpose: Thioredoxin (TRX) is a redox regulatory protein that protects cells from various stresses. Angiotensin-converting enzyme (ACE) inhibitor was reported to enhance endogenous antioxidant enzyme activities. This study was carried out to investigate whether temocapril, a non-sulfhydryl containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX.
Methods and Results: In rats with experimental autoimmune myocarditis (EAM), the protein carbonyl content, a marker of cellular protein oxidation, was increased accompanied with enhanced TRX expression. An immunohistochemical study showed that TRX stain was enhanced in infiltrating inflammatory cells and in damaged myocytes in EAM. The severity of the myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10mg/kg/day, orally) from day 1 to day 21 in which TRX was upregulated when the inflammation started, but were not less increased in temocapril treatment from day 15–21 in which TRX was not upregulated when the inflammation started. Western blot showed that temocapril enhanced cytosolic redox regulatory protein TRX expression, but neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zu-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was increased by the preconditioning treatment.
Conclusions: The results suggest that TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis associated with inducing TRX increase in a preconditioning manner, although the mechanism of TRX induction by temocapril remains to be elucidated.