UC Irvine

ABSTRACT OF THE THESIS

Understanding Neonatal Cardiac Mitochondria Morphology and Structure and the Effect of Macrophage Phenotype on Cardiomyocyte Morphology

By

Jeoung Hyun Kawk

Master of Science in Biomedical Engineering

University of California, Irvine, 2017

Assistant Professor Anna Grosberg, Chair

Neonatal cardiomyocytes are not the most mature form of cardiomyocytes and may contain different structures and morphology compared to those of adult cardiomyocytes. Especially, mitochondrial morphology and structures has not been extensively studied in neonatal cardiomyocytes, leaving the criteria for normal neonatal mitochondrial morphology and structure unclear. Due to this uncertainty, the source of variability, whether it is physiology or external factors, in neonatal mitochondrial morphology and structure could not be accurately assessed. In this study, fixation and/or staining protocols were explored to test their influence on mitochondrial morphology and structure in neonatal cardiomyocyte culture. It was concluded that alterations in PFA concentration and/or incubation time and stain and primary antibody concentrations did not affect mitochondrial morphology and network. In the second part of the study, influence of cytokines in cardiac hypertrophy was investigated by analyzing changes in cell area occurred post introduction of specific cytokines. There are different macrophage populations, and they are often classified into fully polarized states of M1 and M2. M1 macrophages have pro-inflammatory characteristics whereas M2 macrophages have anti-inflammatory characteristics. It was shown that conditioned media obtained from M2 polarized macrophages that contain anti-inflammatory cytokines reduced the cardiomyocyte area, suggesting that cytokines released by M2 can protect and rescue the heart from cardiac hypertrophy. This finding substantiates the capacity of cytokines released from M2 polarized macrophages as possible treatment option for cardiac hypertrophy and adverse remodeling. Although the results regarding the stimulating factors and M1 polarized, or inflammatory macrophages, conditioned media on cardiomyocyte area were unconvincing and not fully understood, this study was successful in validating promising effect of anti-inflammatory cytokines in resolving cardiac hypertrophy.