Calcineurin gene expression level in cardiac hypertrophy

Ji Fang He (2011). Calcineurin gene expression level in cardiac hypertrophy MPhil Thesis, School of Medicine, The University of Queensland.

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Author Ji Fang He
Thesis Title Calcineurin gene expression level in cardiac hypertrophy
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2011-11
Thesis type MPhil Thesis
Supervisor Prof. Malcolm West
Total pages 179
Total colour pages 21
Total black and white pages 158
Language eng
Subjects 11 Medical and Health Sciences
Abstract/Summary Cardiac hypertrophy is an independent risk factor for future morbidity and mortality. Recent investigations have centered on identifying the molecular signaling pathways that regulate cardiomyocyte reactivity that lead to pathologic hypertrophic programs. The calcium sensitive phosphatase calcineurin has been considered to be a potential regulator of cardiomyocyte hypertrophy not only by its phosphatase enzymatic activity but also by its mRNA and protein levels. In this project calcineurin B gene expression level in left ventricular hypertrophic tissue of spontaneously hypertensive rats (SHR) at 5 different time points (neonatal, 2 weeks, 4 weeks, 8 weeks and 12 weeks of age), was compared with levels in normotensive Wistar Kyoto (WKY) rats at the same age groups. A pressure overload cardiac hypertrophy model induced by constriction of the abdominal aorta in WKY rats was also created. Calcineurin B mRNA expression and atrial natriuretic peptide (ANP) mRNA expression were measured after 4 weeks of aortic constriction. Calcineurin B gene expression level in cardiomyocytes was not increased compared to WKY animals. Calcineurin B gene expression level in aortic constricted WKY rats after 4 weeks of pressure overload remained unchanged compared with sham operated WKY rats. Although the results do not exclude activation of the calcineurin-signalling pathway during the development of cardiac hypertrophy there was no increase in mRNA levels in the SHR or pressure overload model during the early stages of hypertrophy development. Regulation by calcineurin may be at a translational level or an alternative signalling pathway may be involved in these animal models. In SHR and WKY rats there was an elevation of calcineurin B mRNA expression in neonatal cardiomyocytes which persisted until 4 weeks of age. Calcineurin may be important for the cardiac morphogenesis during prenatal development. In aortic constricted WKY ANP mRNA levels were increased 4 weeks after application of aortic constriction compared to sham animals. The findings with respect to ANP mRNA are consistent with re-expression of foetal genes in cardiomyocytes associated with pressure overload induced cardiac hypertrophy. There was no activation of calcineurin B mRNA in either a genetic model of cardiac hypertrophy (SHR) or the pressure overload model of cardiac hypertrophy despite the development of cardiac hypertrophy.
Keyword Calcineurin, Gene Expression, Cardiac, Hypertrophy
Additional Notes page 21,25,54-60 and 152-163 should be printed in colour. I would like page 82 and page 96 in landscape please.

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Created: Mon, 21 Nov 2011, 11:34:17 EST by Ji Fang He on behalf of Library - Information Access Service