Gene profiling of pathological cardiac hypertrophy vs physiological hypertrophy

Cardiac hypertrophy can lead to heart failure, and is induced either by physiological stimuli eg postnatal development, chronic exercise training or pathological stimuli eg pressure or volume overload. Majority of new therapies for heart failure has mixed outcomes. A combined mouse model and oligo-array approach are used to examine whether phosphoinositide 3-kinase (p110-alpha isoform) activity is critical for maintenance of cardiac function and long-term survival in a setting of heart failure. The significance and expected outcome are to recognise genes involved in models of heart failure ie pathological- vs physiology-hypertrophy, and examine the molecular mechanisms responsible for such activity. Growth of the heart can be induced by physiological stimuli e.g., postnatal development, chronic exercise training, or pathological stimuli e.g., pressure or volume overload. Physiological hypertrophy (“good”) is characterised by a normal organisation of cardiac structure, and normal or enhanced cardiac function. In comparison, pathological hypertrophy (”bad”) is associated with fibrosis, cardiac dysfunction, and increased morbidity and mortality. The mechanistic process which allows the heart to enlarge in response to physiological stimuli while maintaining normal or enhanced function is of great clinical relevance because one potential therapeutic strategy is to inhibit the pathological growth process while augmenting the physiological growth process. One of the major process that regulate heart size is by phosphoinositide 3-kinase (PI3K). Thus the end goal of this project is to determine whether the p110 alpha isoform of PI3K could be a potential tool for augmenting physiological growth and improving cardiac function of the failing diseased heart, and to examine the underlying mechanisms responsible. Keywords: Disease progression analysis Ntg (nontransgenic), dnPI3K (cardiac-specific transgenic model with reduced PI3K activity) and caPI3K (transgenic mice with increased PI3K activity) mice were used. Mice were divided into MI (myocardial infarction) group and sham (control operation) groups, resulting in 6 experimental groups. 4 arrays were included in each group, each assigned an array number as follows: Ntg sham: 415, 416, 1184. 1185 Ntg MI: 140, 1127, 1174, 1190 dnPI3K sham: 417, 418, 1191, 1181 dnPI3K MI: 228, 1117, 87, 927 caPI3K sham: 1416, 1413, 1417, 1410 caPI3K MI: 257, 261, 1123, 987 The following comparisons were studied: -Ntg sham compared to Ntg MI -caPI3K sham compared to caPI3K MI -dnPI3K sham compared to dnPI3K MI -(Ntg MI-Ntg sham) to (caPI3K MI-caPI3K sham) to (dnPI3K MI-dnPI3K sham) Multiple comparison normalised to Ntg sham.