Modification of gene expression profiling related to renin-angiotensin system in an ischemia/reperfusion rat model after T3 infusion

Abstract

Triiodothyronine (T3) and renin-angiotensin system (RAS) are functionally related in cardiovascular system. Recently, in an in vivo myocardial ischemia/reperfusion (I/R) model in rats, we showed that T3 treatment improved the post-ischemic recovery of cardiac function. In the present study, we used the same experimental model of regional I/R, obtained by 30 min occlusion of the left descending coronary artery, followed by 3-days of reperfusion, to investigate the effect of 48-h treatment (started 1 day after ischemia) with 6 µg/kg/day T3 or vehicle. T3 was delivered by constant subcutaneous infusion via miniosmotic pump. In particular, aim of this work is to evaluate the effects of T3 on the gene expression of the main receptors and enzymes involved in the two cardiac arms of RAS in an in vivo rat model of I/R: AT1R-ACE (detrimental arm) and AT2R/MAS1-ACE2 (protective arm). Gene expression was evaluated by Real-Time PCR in infarct zone (Area-At-Risk: AAR) and in tissues distant from ischemic wound (Remote Zone: RZ). Three different rat groups were used: sham-operated; I/R and I/R + T3. Main result of the study is the opposite response of AT1R and AT2R/MAS1 expression to I/R procedure and to T3 administration after I/R in both AAR and RZ. Moreover, T3 significantly increased ACE and ACE2 enzyme expression in AAR and RZ. This study reveals that T3 stimulates the expression of protective genes related to RAS such as AT2R/MAS1-ACE2 mainly in BZ, suggesting that, at least in part, T3 could be involved in the local cardiac ameliorative response to I/R procedure.

Keywords: Gene expression; Ischemia/reperfusion; Renin–angiotensin system; Triiodothyronine.