Abstract 15653: Heart Failure Medications Have a Direct Inhibitory Effect on Endothelial-to-Mesenchymal Transition in an in vitro Model

Abstract

Introduction: Endothelial-to-Mesenchymal Transition (EndoMT) is a process where endothelial cells can transform into mesenchymal cells. This mechanism, while well established in embryogenesis and cancer, has been accumulating evidence as a contributor to cardiovascular diseases including heart failure (HF). While current guideline-directed medications (GDMT) for HF have postulated benefits to help cardiomyocytes and the heart, further investigation on the specific impact of HF drugs on this pro-fibrotic mechanism of EndoMT is required. Hypothesis: We hypothesize that HF drugs can inhibit EndoMT in an in vitro model Methods: Human umbilical vascular endothelial cells (HUVECs) were incubated for 24 h with the drugs - metoprolol, losartan, lisinopril, dapagliflozin, and valsartan/sacubitril, at concentrations ranging from 1 mg to 1 ng per mL, to evaluate cell viability using alamarBlue TM assay. In vitro EndoMT is induced with Nω-Nitro-L-arginine methyl ester hydrochloride and angiotensin II in HUVECs. During EndoMT, HUVECs were co-incubated with the drugs to determine their effect on EndoMT. Immunofluorescence for Endothelial (VE-Cadherin) and Mesenchymal (Transgelin) markers was used to characterize EndoMT. Results: All the HF drugs tested had a dose-dependent effect on HUVEC viability. The highest drug concentration (1 mg/mL) resulted in cell death while lower concentrations (1 μg to 1 ng per mL) did not affect cell viability. A concentration of 1 μg/mL was used to investigate the drugs’ effect on EndoMT. Immunofluorescence staining revealed reduced levels of expression for Transgelin in HUVCEs induced to undergo EndoMT in the presence of the treated drugs compared to the untreated and vehicle-treated cells after 4 days of incubation. Conclusion All the HF medications inhibited EndoMT in an in vitro model. Our results show that some of the beneficial effects of the HF GDMT medications used in clinical practice could be through an inhibitory effect on EndoMT.