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Cardiovascular Engineering

Cardiovascular Engineering- Poster Session D

Poster T14 - Novel Serotonin-2B Receptor Antagonist Prevents Right Ventricular Hypertrophy

Friday, October 25, 2024
3:30 PM - 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction: Adaptive right ventricular hypertrophy (RVH) is important to maintaining proper cardiac function in response to cases of increased afterload such as pulmonary arterial hypertension (PAH). In PAH, increased pulmonary artery pressures induce an increase in RV afterload that results in enhanced contractility from fibrosis activated RVH. Because RVH transforms overtime into maladaptive RVH which leads to right heart failure (RHF), it is widely debated as to whether it is a beneficial or harmful adaptation. Currently, it is unknown if RVH is necessary to circumvent RHF. Previous research indicates serotonin receptor 2B (5-HT2B) antagonism can be used to treat PAH, however its effects on RVH and RHF have not yet been explored.

Materials and

Methods: In this study, 15-week-old female and male C57BL/6 mice were administered either 50% DMSO/50% PEG400 as a vehicle control, commercial 5-HT2B antagonist SB204741, or our novel 5-HT2B antagonist, VU6062252, via mini-osmotic pumps for 28 days. 1 week after mini-osmotic pump implantation, the mice underwent either sham surgery or pulmonary artery banding (PAB) that lasted 3 weeks.

Results, Conclusions, and Discussions: We found 5-HT2B antagonism significantly reduced Fulton index. From pressure-volume loop data, PAB groups treated with 5-HT2B antagonism exhibited decreased cardiac function and increased contractility compared to the sham group but did not worsen cardiac function when compared to the vehicle control PAB group. These results demonstrate 5-HT2B antagonists, specifically VU6062252, prevent RVH and maintain cardiac function in a PAH model. Future work will expand the use of 5-HT2B antagonism as a potential preventative treatment in RHF.

Acknowledgements (Optional):