[Temocapril treatment upregulated cardiomyocyte thioredoxin expression and improved autoimmune myocarditis].
OBJECTIVE
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 novel non-sulfhydryl containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX.


METHODS
The up-regulation of TRX by temocapril treatment was checked by Western blot in normal rat myocytes in vitro and in vivo, as well as in rats with experimental autoimmune myocarditis (EAM).


RESULTS
Temocapril enhanced cytosolic redox regulatory protein TRX expression, but neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was up-regulated by the preconditioning treatment. In rats with EAM, the severity of myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg x kg(-1) x d(-1), orally) from day 1 to day 21, but not in temocapril treatment from day 15 to day 21. If the characteristics of this model that myocardial inflammation begins around day 15 and keeps on until day 21 is considered, temocapril treatment for 3 weeks might be thought as a preconditioning treatment.


CONCLUSIONS
TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis with inducing TRX up-regulation in a preconditioning manner, although the mechanism of TRX up-regulation by temocapril remains to be elucidated.
Yuan
Zu-yi
ZY
Department of Cardiovascular Medicine, The First Hospital of Xi'an Jiaotong University, Xi'an 710061, China. zuyiyuan@mail.xjtu.edu.cn
Liu
Yan
Y
Kishimoto
Chiharu
C
Shioji
Keioseke
K
Yodoi
Junji
J
Liu
Zhi-quan
ZQ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013482:Superoxide Dismutase / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D013879:Thioredoxins / Q000378:metabolism*; D015854:Up-Regulation
D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; D013879:Thioredoxins; C055603:temocapril hydrochloride; D013482:Superoxide Dismutase