Abstract 14673: Cardiomyocyte Specific Overexpression of Pellino 1 Reverses Sepsis Induced Cardiac Dysfunction in a Murine Model by Reducing Inflammatory Response and Cardiac Cell Death
| Autor: | Diego Accorsi, Seetur R. Pradeep, Santosh Swaminathan, Nilanjana Maulik, Mahesh Thirunavukkarasu, J. Alexander Palesty, Jacob Campbell, Rickesha I Wilson |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Circulation. 142 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Introduction: Sepsis remains a significant cause of mortality in the intensive care unit till today. Recent research suggests nearly one in four deaths in people with heart failure is caused by sepsis. Overexpression of mammalian Pellino-1 (Peli1), a E3 ubiquitin ligase, causes inhibition of apoptosis, oxidative stress, and preservation of cardiac function in a myocardial infarction model. Therefore, in the present study, we explored the possibility to overcome sepsis mediated heart failure by overexpressing Peli1 (AMPEL1Tg/+) in a mouse model of severe sepsis. Methods: C57BL/6J (WT) and AMPEL1 Tg/+ mice were divided into Wild-type sham (WTS), Wild-type Cecal Ligation and Puncture (WTCLP), AMPEL1 Tg/+ sham (AMPEL1 Tg/+ S) and AMPEL1 Tg/+ CLP. Cardiac function (LVEF, FS) by two-dimensional echocardiography was assessed pre-procedure, at 6, and 24 hours post-surgery. Serum IL-6 and TNF-alpha (ELISA) at 6 hours and cardiac apoptosis (TUNEL assay) at 24 hours were measured. Results are expressed as mean ± SEM. Results: Analysis of echocardiographic parameters (EF, FS) preoperatively and among the sham groups were similar however there was significant preservation of post-procedure LVEF (%) in the AMPEL1 Tg/+ CLP at the 6 hour (AMPEL1 Tg/+ :52.7 ± 3.71 vs WT:40.7 ±2.46, p=0.013, n=10-11) and 24-hour time point (AMPEL1 Tg/+ :63.1 ± 1.63 vs WT:49.3 ± 4.41, p=0.002, n=9-11) compared to WT. Similar trend was observed in estimation of FS (%) at 6 hours (AMPEL1 Tg/+ :26.3 ± 2.22 vs WT:19.3 ±1.37, p=0.014, n=10-11) and 24 hours (AMPEL1 Tg/+ :32.4 ± 1.89 vs WT:24.4 ± 2.67, p=0.031, n=9-11). A marked decrease in serum IL-6 (AMPEL1 Tg/+ :259.7 ± 18.70 vs WT:483.2 ± 24.01, pTg/+ :86.89 ± 14.36 vs WT:161.8 ± 20, p=0.012, n=6, pg/mL) was observed in the AMPEL1 Tg/+ CLP at 6 hours. The preserved cardiac function in CLP was further supported by a noticeable decrease in cardiac apoptosis (% TUNEL positive cells) at 24 hours in the AMPEL1 Tg/+ CLP group (4.7 ± 0.94 vs 11.7 ± 2.82, p=0.040, n=6,) compared to WTCLP. Conclusions: Thus, Peli1 overexpression is a novel approach that preserved cardiac function, reduced inflammatory markers, and apoptosis following severe sepsis in a murine genetic model. |
| Databáze: | OpenAIRE |
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