P562Increased expression of antioxidant enzymes, pro-survival and apoptosis genes in diseased ventricle of coronary heart disease patients

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Abstract

It is thought that patients with ischemic heart disease, through preconditioning of the heart, have increased protection from ischemia-reperfusion injury. An experimental mouse model of coronary artery disease demonstrates increased resistance to ischemia and reperfusion injury and shows increased survival signalling through Akt phosphorylation. This study aims to determine whether increased survival signalling can also be observed in patients with coronary artery disease.

Left (diseased) and right (control) ventricular biopsies were taken before aortic cross clamp from patients undergoing coronary artery bypass graft surgery (CABG, n=4). RNA from biopsies was extracted using trizol. Markers of survival signalling and apoptosis were quantified by TaqMan PCR and normalised using 18S ribosomal RNA. Results were expressed as fold changes (FC) between diseased and control ventricle and significance was taken as p < 0.05 (paired t-test).

Evidence of increased survival signalling was observed in the diseased left ventricle (LV) compared to the control right ventricle as shown by significant elevation in heat shock protein 90 (HSP90, FC: 2 fold), protein phosphatase 2A regulatory subunit B (PP2A3B, FC: 2.7), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (PIK3R2, FC: 1.5) and the anti-oxidant enzyme glutathione peroxidase 1(FC: 1.8 fold). The apoptotic related factor c-Jun is significantly more highly expressed (FC: 3.9) and the apoptotic factor caspase-3 shows a trend of increased expression (FC: 2.9) within the ischemic LV.

From this study it is evident that survival signalling is increased at the gene level in the coronary disease ventricle compared to the right ventricle. Whether these changes are also occurring at the protein level requires further investigation.

This work was approved by the local ethics committee with all patients giving consent.

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