Up-regulation of endothelin-converting-enzyme mRNA expression following cardioplegic arrest

Abstract

Endothelin-1 (ET-1) is believed to play an important role in cardiac ischaemia/reperfusion injury. ET-1 is synthesized from preproET-1 by the action of ET-converting enzyme (ECE). It is unclear to what extent the ET system is activated following prolonged ischaemia. In this study we used a model mimicking the conditions of the donor heart during transplantation. Isolated rat hearts perfused with Krebs-Henseleit buffer were subjected to 30 min of normothermic perfusion, then 4 h of cardioplegic arrest at 4 degrees C with St Thomas' Hospital solution, followed by reperfusion for 2 h. Hearts were freeze-clamped at different time points during the protocol. Using quantitative reverse transcription-PCR, relative levels of ET-1 and ECE mRNA expression were measured and compared with a housekeeping gene (ribosomal protein L32). During reperfusion there was a consistent decrease in coronary flow to approx. 85-90% of pre-ischaemic flow. There was no significant alteration in preproET-1 mRNA expression during 2 h of reperfusion. However, ECE mRNA expression was increased by 77.5% at 1 h and by 74.6% at 2 h following ischaemia compared with pre-ischaemic values (P<0.05). Thus we conclude that ECE mRNA expression is increased following prolonged hypothermic cardioplegic arrest. Elevations in the expression of this enzyme may help to explain the role of the ET system in the pathogenesis of ischaemia/reperfusion injury following cardiac surgery and transplantation.

Comparative Analysis of Preservation Method and Intermittent Perfusion Volume on the Expression of Endothelial and Inflammatory Markers by Coronal Artery and Myocardium in Porcine Donor Hearts

“…*p < 0.01, significantly different from the control group; † ‡p < 0.01, significantly different from the †50 and ‡100 ml intermittent perfusion groups, respectively. Because ET-converting enzyme (ECE) may also be associated with ischemia/reperfusion injury after cardiac surgery and transplantation, 36 further studies will also analyze ECE levels after intermittent reperfusion.…”

Tyrosine aminotransferase is involved in the oxidative stress response by metabolizing meta-tyrosine in Caenorhabditis elegans

“…Most notably, DAVID functional annotation highlighted the ribosome as being affected by the F01D4.5 mutation, and specific isoforms of multiple genes encoding ribosomal large subunit proteins were down-regulated. This is surprising, considering the previous usage of some of them as reference genes in certain species (63,115,116); however, the down-regulation of the expression of these isoforms of ribosomal proteins may suggest a potential diminution of ribosome production, mRNA translation, and ultimately protein synthesis. Indeed, there is evidence from previously published work reporting that the reduced expression of ribosomal subunits results in a reduction of protein synthesis.…”