Poster abstracts
Poster number 11 submitted by Ashley Francois
The effect of global Sertad4 KO on post-MI cardiac remodeling
Ashley Francois (Molecular, Cellular and Developmental Biology MCDB ), Lynn Marcho (Department of Physiology & Cell Biology, Ohio State University ), Erin McGrail (Department of Physiology & Cell Biology, Ohio State University ), Alessandro Canella (Department of Physiology & Cell Biology, Ohio State University ), Paul Janssen (Department of Physiology & Cell Biology, Ohio State University ), Richard Gumina (Department of Internal Medicine, Ohio State University )
Abstract:
Heart failure (HF) affects millions of adults in the US and is prevalence is projected to increase 46% by 2030. HF is characterized by the heart's inability to sufficiently perfuse the body, resulting in edema, pulmonary congestion and multiorgan dysfunction. One common cause of HF is myocardial infarction (MI). At the ischemic site of damage, activated fibroblasts help establish a stabilizing scar. However, fibroblast activation can extend beyond the damaged area and cause excess deposition of extracellular matrix in previouslt healthy areas, leading to HF and possible death. The nuclear protein, Sertad4 (SERTA domain-containing protein 4) is a member of the SERTAD family of proteins, characterized by a conserved SERTA domain. Other members of this family have been identified as cell cycle regulators and transcriptional co-factors, but little is known about the role of Sertad4. In 2019, cell culture experiments identified Sertad4 as a potential regulator of cardiac fibroblast activation and we have observed increased protein expression of Sertad4 in human ischemic heart failure samples. We sought to determine the effect of a global Sertad4 knockout on post -MI cardiac remodeling in mice. After 4 weeks of permanent LAD ligation, echocardiography was performed to measure systolic function. Relative to wild-type controls, the Sertad4 KO mice showed preserved systolic function as evident by improved ejection fraction and fractional shortening. B-Gal staining in the Sertad4/LacZ reporter also showed robust Sertad4/LacZ expression in the infarct scar which extended into non ischemic tissue. This data supports the notion that Sertad4 has a key role in cardiac remodeling in response to ischemic injury. Future directions include investigating Sertad4 in cardiac inflammation, investigation Sertad4 molecular mechanisms, and cell-type specific disruption of Sertad4.
Keywords: cardiac