Abstract 527: The Functional Significance of the Adenosine A 2b Receptor in the Internal Mammary Artery

Objective: The endothelium is the initial target that leads to cardiovascular disease. Knowing that the internal mammary arteries (IMA) are resistant to the development of atherosclerosis, which contrasts with coronary arteries (Cor) which are athero-prone, we hypothesize that genes over-expressed in the endothelial cells (ECs) of between these two arteries will identify genes that resist atherosclerosis. Methods and Results: Microarray analysis showed over 1,000 differentially expressed in the ECs of IMA vs Cor. The most statistically significant different gene was the adenosine A 2B receptor. This indicates the A 2B receptor may be involved in a resistance to atherosclerosis. Western blot analysis showed higher A 2B expression in the IMA than in coronary arteries with or without disease from proteins harvested from these human arteries and ECs. Overexpression of A 2B in ECs blunted: monocyte adhesion, cell adhesion molecule expression, migration, and the transendothelial migration of monocytes-- processes directly associated with the development of atherosclerosis. Knockdown of A 2B expression by siRNA promoted these processes. Conclusions: ECs derived from the IMA and Cor are distinctly different in gene expression, which may be responsible for their differential sensitivities for atherosclerosis. This study defined how the A 2B receptor may act as an atherosclerotic-resistance gene, which blunted monocyte adhesion and cell adhesion molecule expression, EC migration and retarded the transendothelial migration of monocytes.