Jacqueline Spangenberg

Jacqueline Spangenberg

PI: Jason Becker, MD, Department of Cardiovascular Medicine

Investigating the Role of MYBPC3 in Murine Cardiomyocyte Growth

Hypertrophic cardiomyopathy is a condition involving the enlargement of the heart muscle, resulting in functional defects of the heart. Mutations in the sarcomere protein, cardiac myosin-binding protein 3 (MYBPC3), are a common cause of hypertrophic cardiomyopathy in humans. Hypothesis: We hypothesize that cardiomyocytes lacking MYBPC3 protein would be larger than cardiomyocytes with normal levels of MYBPC3 protein. Methods: We utilized a transgenic murine model that exhibits a mosaic of cardiomyocytes that express or lack MYBPC3 protein. We performed immunohistochemistry of the MYBPC3 protein to identify which cardiomyocytes expressed MYBPC3 protein. In addition, we performed wheat germ agglutinin (WGA) staining to identify the cardiomyocyte cell border. We then measured the cross-sectional areas of MYBPC3-positive and MYBPC3-null cardiomyocytes. The average number of cardiomyocytes analyzed per heart was approximately 1,000 cardiomyocytes. We analyzed post-natal day 25 murine hearts (n=4). Results: The average cross-sectional area for cardiomyocytes that expressed MYBPC3 protein was 153.19 (+/-5.25) μm2 and 138.29 (+/-3.88) μm2 for cardiomyocytes that did not express MYBPC3 protein (p=0.039). Conclusion: These data indicates that the absence of MYBPC3 expression may not be responsible for cardiomyocyte hypertrophy in a normally functioning heart. These results provide us additional insight into how cardiomyocytes respond to alterations in the expression of MYBPC3 protein and are important in our understanding of the mechanism responsible for hypertrophic cardiomyopathy.