Abstract 14445: Cytoprotective Role of Beta Blockers via Heat Shock Protein 70 Expression in the Human Aorta During Cardiac Surgery
The aortic wall appears to be the site of the most dramatic expression of heat shock proteins (HSP), especially after surgical stress. The objective of this study was to elucidate the expression and function of aortic HSP70 in patients undergoing coronary surgery. We examined 24 consecutive patients undergoing coronary artery bypass grafting. The patients group was made up of 4 women and 20 men with a mean age of 61+/-1.5 years (range 44 to 73 years). The study was approved by the ethics committee, and informed consent was obtained. The pieces of the aortic wall, which were removed in order to perform the proximal anastomoses were used for Western blotting, real time RT-PCR or immunostaining. Coimmunostaining of the aortic wall with the smooth muscle cell marker smooth muscle α actin demonstrated HSP70 expression was localized to the aortic smooth muscle cells. Western blot analysis and real time RT-PCR confirmed HSP70 protein and mRNA expression in the aortic wall respectively. Ischemic time and the administration of adrenergic beta antagonists influenced HSP70 expression in the aorta. There was a linear relationship between ischemic time and HSP70 expression in the subgroup of patients treated with adrenergic beta antagonists (p=0.00007, r=0.895 and p=0.0004, r=0.782 respectively). Real time RT-PCR and Western blot analysis confirmed an approximate 2 fold increase in HSP70 mRNA and protein in the aortic wall of patients receiving chronic beta blockade with metoprolol versus patients not on beta blockers. Patients on beta blockade had less smooth muscle cell apoptosis as measured by caspase activity (63.9+4.3 (-β blockade) versus 51.6+2.9 (+β blockade), μmol/ml, p<0.05), TUNEL staining [0.012+0.003 (-β blockade) vs. 0.005+0.001 (+β blockade) % apoptotic smooth muscle cell nuclei, p<0.05] and the apoptotic gene ratio bax(proapoptotic)/bcl 2(antiapoptotic) (approximate 50 per cent decrease). The delayed induction of HSP70 in the smooth muscle cells of the aortic wall of patients with coronary artery disease, following surgical stress is more pronounced in patients receiving beta blockade and is associated with less apoptosis a condition resembling preconditioning of the aortic wall.
- © 2012 by American Heart Association, Inc.