Abstract 387: Individual Biochemical Characterization of the Renin-Angiotensin-System by RAS-Fingerprinting in Healthy Volunteers Treated with RAS-Blockers

Abstract

The Renin-Angiotensin-System (RAS) is critically involved in the regulation of important physiological functions including blood pressure and fluid balance. It is constituted by multiple enzymes giving rise to a meshwork of effector peptides, which mediate their functions through binding to specific receptor molecules. Therefore, the modification of angiotensin peptide levels represents a common strategy for the treatment of RAS-associated diseases and is frequently achieved by the pharmacologic regulation of enzymes taking part in angiotensin metabolism. We developed a highly sensitive method, which allows the simultaneous absolute quantification of up to 10 different angiotensin peptides in human plasma and whole blood (RAS-Fingerprinting). The measurement of RAS-Fingerprints provides unique insights into the physiology of the human RAS and therefore represents a powerful tool for the patient specific evaluation of this physiologically important peptide hormone system. Beside the precise quantification of angiotensin peptides in plasma and whole blood, RAS-Fingerprints analyze the biochemical hardware of the RAS at a previously unachieved level of detail and accuracy. During the development and validation of our LC-MS/MS based method, comprehensive datasets showing multiple applications for RAS-Fingerprinting have been generated. Investigation of healthy volunteers revealed that a patient specific state of the RAS exists, which is defined by a unique composition of RAS enzyme activities that might have crucial effects on the outcome of RAS targeted therapies in individual patients. RAS-Fingerprinting in healthy volunteers treated with an Angiotensin-Receptor-Blockers, ACE-Inhibitor or Renin-Inhibitor revealed that the human RAS reacts to different drugs in a very dynamic and specific way. Therefore, RAS-Fingerprinting could contribute to the development of innovative therapeutic approaches affecting the RAS. The implementation of RAS-Fingerprinting into clinical studies would substantially enhance our understanding of the human RAS and could lead to the development of personalized treatment schemes in the management of RAS-associated diseases in the near future.