Karen Jin
Pronouns: she/her
Research Mentor(s): Adam Helms
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine / Cardiovascular Medicine / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 2 – 11am – 11:50am
Room: League Ballroom
Authors: Karen Jin, Eric Smith, Sabrina Friedline, Adam Helms
Presenter: 5
Abstract
Desmoplakin cardiomyopathy is a form of arrhythmogenic cardiomyopathy characterized by cardiac fibrosis, left ventricular systolic dysfunction, and arrhythmias. Desmoplakin, encoded by the DSP gene, is found in desmosomes, which are critical in anchoring intermediate filaments and maintaining the structural integrity of intercellular contacts in cardiac and epidermal tissue. Complete loss of desmoplakin results in severe epidermal abnormalities and early fetal death. To better understand the pathogenic mechanisms that relate to mutations in DSP, a haploinsufficient murine model with deletion of exon 3 and flanking splice sites was created using CRISPR technology. We hypothesized that haploinsufficient mice would demonstrate significant cardiac fibrosis and systolic dysfunction. To assess for cardiac fibrosis, left ventricular cross sections from wild type and heterozygous DSP knockout mice at 3 and 6 month time points were stained with fast green and picrosirius red. Cardiac fibrosis was quantified as the percentage of the image containing collagen. To further exacerbate cardiac injury, mice were injected with epinephrine and isoproterenol at various dosages to induce a catecholaminergic challenge, which has previously been shown to selectively induce cardiac injury in a muscular dystrophy murine model. The adrenergic challenge is predicted to cause left ventricular dilation, cardiac inflammation, and systolic dysfunction. Cardiac chamber sizes and function were assessed with echocardiography pre and post injection. Inflammation is being quantified as the presence of IgG and cells positive for CD45 in myocardial cross sections. The results of this study will quantify cardiac inflammation and fibrosis in a murine DSP model, which will be used in the future to better understand desmoplakin cardiomyopathy in humans and lay the foundation for possible therapeutic targets.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
