Pharmacological inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and the biomechanical tissue properties of healing and scarred myocardium
Mentor:Francisco Villarreal, M.D, Ph.D, University of California San Diego
The inhibition of the 11βHSD1 enzyme has been recognized as a novel therapeutic target after MI. The ongoing study investigates the hypothesis that the pharmacological inhibition of the 11βHSD1 enzyme will improve the biomechanical tissue properties of healing and scarred myocardium. For this study, hearts from normal and infarcted (short and long term) mice are used either untreated or treated with 11βHSD1 inhibitor compounds. To evaluate the biomechanical tissue properties, we arrest mouse hearts, excise them, and place them onto an infusion system attached at the level of the mitral valve to a small cannula and balloon which is used to inflate/deflate the left ventricle. We paint three dots onto the myocardial region of interest and, during the inflation/deflation, we record the displacement of the dots to later transform their movement into two dimensional epicardial strains. We expect that tissue from animals subjected to a pharmacological inhibition of 11βHSD1 will evidence improved biomechanical properties in comparison with untreated animals. This would validate the use of 11βHSD1 inhibitor compounds to enhance biomechanical properties of healing and scarred myocardium.