UC Irvine

Cardiovascular diseases remain the leading cause of death worldwide, necessitating researchto tackle the multitude of pathologies within the cardiovascular system. The zebrafish model (Danio rerio) is an intriguing animal model for cardiovascular research because of its similar homology to humans, ample genomic knowledge with orthologous genes, ease of maintenance, and regenerative capability. Therefore, the zebrafish model is applicable for various cardiovascular pathologies, including drug response, electrophysiological analysis, genetic characterization, and strategies for future cardiac treatments. The work outlined in this dissertation presents several of these applications. An ECG (electrocardiogram) system suitable for elucidating drug response and genetic function was developed, and validation was performed to demonstrate the capability of the system, including dose-response experiments and phenotyping mutations pertinent to electrophysiology. An in-depth analysis of how methamphetamine may affect abnormal electrophysiological phenotypes was conducted, and an underlying genetic mechanism for causing such abnormalities was proposed. Finally, a system was developed to investigate how inducing hypoxia, the condition of low oxygen concentration, may modulate the hypoxia genetic pathway. This carries implication on elucidating the intrinsic regeneration process in zebrafish. Overall, the work presented in this dissertation provides contribution in promoting the zebrafish model in the multifactorial facets of cardiovascular diseases and drug screening.