Abstract 8682: Microarray and Proteomic Analysis of Cardioprotection in the Mature and Aged Male and Female: Role of the Mitochondrion and Mitochondrial Pathways
Background: Recently we have shown that cardioprotection afforded by cardioplegia is modulated by RNA and protein dependent mechanisms and is significantly decreased with age and in particular is significantly decreased in the aged female, however, the pathways associated with these differences were unknown.
Methods: Mature male and female (15 to 20 weeks; n=6 each) and aged male and female (>32 months; n=6 each) New Zealand White rabbits were used for in situ blood perfused cardiopulmonary bypass (CPB). Control hearts received 30 min sham global ischemia (GI) and 120 min sham reperfusion. GI hearts received 30 min GI, achieved by crossclamping of the aorta. Cardioplegia hearts received cold blood cardioplegia prior to GI. Following 30 min GI the crossclamp was released and the hearts were reperfused for 120 min. RNA and proteins were isolated and microarray and proteomic analysis was performed on matched samples.
Results: Microarray analysis showed that cardioplegia up-regulated genes for transcription and the mitochondrion in mature male and female hearts and cytoskeleton dependent intracellular transport and cell-substrate function in aged male and female hearts. Proteomic analysis identified 362 proteins of which 132 were common to all groups. Principal component analysis indicated differential protein expression in each treatment in the mature male and female and aged male, but in the aged female there was no difference in the proteins expressed during GI and cardioplegia. Cardioplegia up-regulated glycolytic and gluconeogenic pathways in the mature and aged male and oxidative phosphorylation, the electron transport chain, propanoate and pyruvate metabolism and the induction of apoptosis in the mature and aged female. The tricarboxylic acid cycle was uniquely up-regulated by cardioplegia in the aged female but not glycolysis or gluconeogenesis.
Conclusions: These data demonstrate that the mitochondrion and mitochondrial pathways play a key role in age and gender specific cardioprotection. The identification of these specific pathways will allow for the development of age and gender specific cardioprotection which should significantly decrease morbidity and mortality in the aged female undergoing open heart surgery.
- © 2011 by American Heart Association, Inc.