Abstract 227: Activation of Angiotensin II Type 2 Receptor Suppresses TNFα-induced ICAM-1 via NF-κB: Possible Role of ACE2

Activation of the renin-angiotensin system (RAS) is a major factor contributing to the pathophysiology of cardiovascular disease (CVD). Blockade of the RAS with angiotensin receptor blockers (ARBs) has been a standard treatment for CVD. Activation of angiotensin II type 2 receptor (AT2) and angiotensin I-converting enzyme 2 (ACE2) contribute to the cardioprotective effects of ARBs. Both AT2 and ACE2 counteract the vasoconstrictor and pro-inflammatory effects of angiotensin II. However, the possible interaction between AT2 and ACE2 has never been established. Tumor necrosis factor (TNFα) is a cytokine involved in angiotensin II signaling and promotes the inflammatory response via NF-κB. We hypothesized that activation of AT2 increases ACE2, thereby preventing TNFα-stimulated intercellular adhesion molecule-1 (ICAM-1) expression via inhibition of NF-κB. Human coronary artery endothelial cells were pretreated with AT2 antagonist PD123319 or ACE2 inhibitor DX-600, and then stimulated with TNFα in the presence...