Influence of gene expression on the development and progression of atherosclerosis

摘要

This investigation aimed to compare gene expression differences between atheroresistant (brachial) and atherosusceptible (femoral) arteries in 13day old Rapacz HC swine, as well as identify gene expression associated with the initiation and progression of peripheral atherosclerosis in the same arteries of one and two year old Rapacz HC swine. Methods: A paired t-test was used to compare gene expression of healthy brachial and femoral arteries in the 13day old Rapacz HC swine. A 2x2 ANOVA was used to analyze the arteries from one and two year old Rapacz HC swine. Disease phenotype was quantified using Sudan IV, H/E, and VVG staining. Hypotheses: We hypothesized that gene expression differences between healthy brachial and femoral arteries in the 13day old Rapacz HC swine will contribute to the uneven atherosclerotic disease distribution later in the animal's life. In addition, we hypothesized that gene expression differences will diverge in one and two year old animals due to an increase in disease in the femoral but no lesion formation in the brachial artery. Results: Healthy arteries from the 13day old Rapacz HC swine showed a total of 366 significantly different expressed probe sets between the atheroprotected and atherosusceptible artery. Analysis of these probe sets is the first evidence that gene expression differences could contribute to the uneven disease distribution later in life. A total of 184 probe sets were identified by the ANOVA as having a significant age*artery interaction. In addition BLAST identified that these probe sets are very similar to genes involved in known atherogenic pathways. Interestingly, contrary to our hypothesis the number of differently expressed genes decreased with increasing disease in the femoral artery.