Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: E141
Jacob Russell (University of Missouri, Harry S. Truman Memorial Veterans Hospital), Chastidy Bailey (University of Missouri, Harry S. Truman Memorial Veterans Hospital), Scott Brown (University of Missouri, Harry S. Truman Memorial Veterans Hospital), Vincent DeMarco (University of Missouri, Harry S. Truman Memorial Veterans Hospital, Dalton Cardiovascular Center), Srinivas Mummidi (South Texas Diabetes and Obesity Institute), Shawn Bender (University of Missouri, Harry S. Truman Memorial Veterans Hospital, Dalton Cardiovascular Center), Bysani Chandrasekar (University of Missouri, Harry S. Truman Memorial Veterans Hospital, Dalton Cardiovascular Center)
Presenting Author University of Missouri, Harry S. Truman Memorial Veterans Hospital
Introduction: Excess and chronic activation of the sympathetic nervous system often results in progressive adverse remodeling and heart failure development. Here we investigated whether chronic administration of isoproterenol (Iso), a β-AR agonist, would promote hypertrophy, fibrosis, and dysfunction, and whether these maladaptive changes are prevented by minocycline, an FDA-approved antibiotic, that has been shown to have cardioprotective effects outside of its antibacterial properties.
Methods: Wild-type male C57BL/6J mice were subcutaneously implanted with osmotic minipumps, delivering either 30 mg/kg body weight per day of isoproterenol, or vehicle control. Following pump implantation, mice received daily intraperitoneal (I.P.) injections of either sterile saline or 50 mg/kg of minocycline. After 21 days, cardiac function was assessed by echocardiography, and hearts were collected for further analysis. A transverse slice of the ventricles was fixed for histology, and a portion of the left ventricle was used for RNA isolation, and mRNA and miRNA sequencing.
Results: Echocardiography revealed that isoproterenol increased heart rate, heart weight (hypertrophy), ejection fraction and fractional shortening, without leading to significant changes in fibrosis. Minocycline prevented the hypertrophic remodeling and changes in systolic function without affecting heart rate. While mRNA sequencing revealed that isoproterenol enriched gene networks associated with changes in inflammation, the miRNA sequencing showed that minocycline enhanced miR-26b expression, which is reported to suppress GATA4-mediated hypertrophy.
Conclusion: Minocycline mitigates isoproterenol-induced cardiac hypertrophy while preserving contractility, as well as induces changes in RNA and miRNA pathways involved with inflammation and cardiac remodeling
This study was supported by grants from the US Department of Veterans Affairs (VA-I01-BX004220) and Research Career Scientist (IK6BX004016) to BC. SBB is supported by NIH R01 HL136386. This work was supported by the use of facilities and resources at the Harry S. Truman Memorial Veteransamp;rsquo;amp;rsquo; Hospital in Columbia, MO.
