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Genomics III: Methods, Techniques and Applications
Title
Genomics III: Methods, Techniques and Applications
Editor
iConcept Press
Price
USD$139.00
ISBN
978-1-922227-416
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17839

Chapter 3

Genomics III: Methods, Techniques and Applications

Whole Genome Microarray Gene Expression Profiling of Atherosclerosis Genes after Treatment with Captopril

by Joshua Abd Alla and Ursula Quitterer

Viewed: 1258

Abstract

Whole genome microarray gene expression profiling is a powerful method to investigate pathomechanisms of disease. Atherosclerosis and cardiovascular disease are the major cause of death in industrialized countries and treatment options are limited. We applied the microarray technique to study pathological gene expression during atherosclerosis development and treatment. As a model system we used hypercholesterolemic apolipoprotein E-deficient mice, which develop atherosclerotic lesions of the aorta and mimic many features of atherosclerotic vascular disease of patients. Pharmacological treatment was performed with captopril, an inhibitor of the angiotensin-converting enzyme (ACE), because inhibition of the vasoactive angiotensin II system retards the progression of atherosclerosis in animal models and patients. We present here that whole genome microarray gene expression profiling identified disease-related genes, which were differentially expressed in the atherosclerotic aorta relative to the control aorta. Comparative microarray data analysis revealed that more than 250 of differentially expressed probe sets were normalized upon atherosclerosis treatment with the angiotensin II inhibitor. Gene ontology analysis of microarray data showed that the ACE inhibitor captopril normalized specifically the expression of genes related to the recruitment of pro-inflammatory immune cells into the walls of the aorta. Validation of micrarray data was performed by immunohistology and immunoblotting, confirming that captopril treatment specifically reduced the migration of proinflammatory monocytes and T-cells into the atherosclerosis-prone aorta. The pro-inflammatory CC-chemokine CCL25 and its receptor CCR9 were causally related to atherosclerotic plaque development because down-regulation of CCR9 in immune cells by RNA interference (RNAi) reduced atherosclerotic lesions. Moreover, atherosclerotic lesions of patients with coronary artery atherosclerosis showed also increased infiltrates of CCR9-positive cells. Taken together an integrated approach of whole genome microarray gene expression profiling combined with biochemical and transgenic techniques identified CCR9 as a novel disease-relevant target gene.

Author Details

Joshua Abd Alla
ETH Zürich, Switzerland
Ursula Quitterer
ETH Zürich, Switzerland

Citation

Joshua Abd Alla and Ursula Quitterer. Whole Genome Microarray Gene Expression Profiling of Atherosclerosis Genes after Treatment with Captopril. In Genomics III: Methods, Techniques and Applications. ISBN:978-1-922227-416. iConcept Press. 0000.

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