Abstract 629: Differential Expression Of Angiotensin-(1-12)/chymase In Human Atrial Tissue

Abstract

Proangiotensin-12 [Ang-(1-12)] is a C-terminal extended form of Ang I [Ang I-Leu-Tyr] originally isolated from the rat small intestine. Additional studies showed that while both ACE and chymase cleaved Ang II from Ang-(1-12) in the rat heart, chymase but not ACE metabolized Ang-(1-12) in the human heart. This study characterized the expression of Ang-(1-12)/chymase in human atrial tissue to gain an insight into the potential role of this Ang II-forming substrate in cardiac disease. Left (LA; n=16) and right (RA; n=14) portions of atrial appendages were obtained from humans undergoing heart surgery. Quantitative Ang-(1-12) immunohistochemistry (Image J software) was performed using a high affinity purified antibody directed to the COOH-terminus of the full length of human Ang-(1-12) in all samples (LA: male=13 and female=3; RA: male=9 and female=5). Chymase activity was determined by HPLC in plasma membranes from left (males=7 and females=3) and right atria (males=7 and females=3). Quantitative analysis of Ang-(1-12) expression revealed significantly higher Ang-(1-12) expression in LA (Intensity: 35.37±6.24 units) versus RA (19.38±2.38 units, p=0.03) appendages. Likewise, chymase activity was higher in the LA (52.02±5.20 fmol/mg/min) compared to RA (18.09±3.05, p<0.0001) tissues. Expression of Ang-(1-12) in atria did not correlate with subject’s age, disease process or medications. The novel demonstration of higher Ang-(1-12) expression and chymase activity in human LA reveals a critical role of this tissue Ang II forming axis in modulating the diastolic and systolic properties of this cardiac cavity.