Ischemic cardiomyopathy affects the thioredoxin system in the human myocardium.

BACKGROUND: Oxidative stress due to reactive oxygen species (ROS) production is one key factor in the development of heart failure (HF). The present study investigated the thioredoxin (Trx) system, which plays a major role in antioxidant defense, in patients suffering from ischemic (ICM) or dilative cardiomyopathy (DCM).

METHODS: Myocardial tissue from ICM (n=13), DCM (n=13) as well as septal tissue of patients with aortic stenosis but without diagnosed hypertrophic cardiomyopathy and subaortic stenosis (control, n=12) was analyzed for Trx1, Trx-interacting protein (TXNIP) and E3-ligase ITCH expression. Trx-reductase 1 (TXNRD1) amount and activity, cytosolic cytochrome c content and apoptosis markers were quantified by ELISA and multiplexing.

RESULTS: Compared to controls, ITCH and Trx1 expression, TXNRD1 amount and activity were reduced and TXNIP expression was increased in ICM (ITCH: p=0.013; Trx1: p=0.028; TXNRD1 amount: p=0.035; TXNRD1 activity p=0.005; TXNIP: p=0.014) but not in DCM. A higher level of the downstream apoptosis marker caspase 9 (ICM: 582 ± 262 MFI, pto control = 0.995, DCM: 1251 ± 548 MFI, pto control =0.002, control: 561 ± 214) was detected in DCM tissue. A higher expression of Bcl-2 was found in DCM (p=0.011).

CONCLUSION: The Trx system was impaired in ICM but not in DCM. ITCH appeared to be responsible for the downregulation of the Trx system. ROS-induced mitochondrial instability appeared to play a role in DCM.