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Department of Molecular Biology

College of Agriculture and Natural Resources


Statement of Research Interest

Molecular and Cellular Responses to Acute Myocardial Infarction

Cardiovascular disease is the single largest cause of death in westernized societies and the cost to treat acute myocardial infarction (AMI) in the United States alone is ~$5 billion per year.  For a given patient, predicting the risk of a future adverse cardiovascular event is difficult, despite family history and the use of clinical markers such as plasma lipid levels and protein markers of inflammation.  As a result, physicians and patients must make equivocal, and often expensive, therapeutic decisions based on incomplete information.  Furthermore, patients are frequently resistant to changing high-risk lifestyle habits, particularly when the danger seems remote or unspecified.

We are part of a multidisciplinary group* that is exploring molecular responses to AMI in a mouse surgical model.  We carry out open-heart surgery on mice and tie off the left anterior descending coronary artery thus inducing an acute myocardial infarction.  At intervals out to 48-h, we sacrifice the mice and measure 36,000 transcript concentrations in blood and three regions of the heart using Affymetrix mouse GeneChips.  As a control, we carry out a parallel time course analysis in mice which have undergone surgery, but without ligation of the coronary artery.  By comparing gene expression patterns between ischemic/infarcted mice and sham surgery controls at selected time points, we are developing models that classify LV myocardial gene expression patterns in response to ischemia and subsequent infarction.

Using the database as a starting point, we are addressing questions that include:  1) Do previously unrecognized genes play a role in the response of the left ventricle ( LV ) to infarction? 2) Can alterations in transcriptional processes be used to distinguish among signal transduction pathways that trigger the LV remodeling response? (3) Can the database be used to construct a comprehensive model for the matrix of reactions and their temporal expression that constitute the tissue response to infarction?  We are testing hypotheses derived from this expression database using the tools of biochemistry and cell biology and employing knock-out and transgenic mice.

*with the Department of Animal Science and the Department of Kinesiology and Health

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