PhD Scientific Days 2026

Pharmaceutical Sciences and Health Technologies 1.

Cardiovascular Safety of Vista Immune Checkpoint Inhibition: Evidence from Human Heart Failure and Murine Models

Name of the presenter

Jakab, Márk

Institute/workplace of the presenter

Departement of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary

Authors

Márk Jakab^1,2, Zsombor I. Hegedűs^1,2,3, Tamás Gergely^1,2,3, Péter Ferdinandy^1,3,4, Zoltán V. Varga^1,2,3
1: Center for Pharmacology and Drug Research and Development, Semmelweis University, Budapest, Hungary
2: MTA-SE Momentum Cardio-Oncology and Cardio-Immunology Research Group, Budapest, Hungary
3: Departement of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
4: Pharmahungary Group, Szeged, Hungary

Text of the abstract

Introduction: VISTA is a next-generation immune checkpoint undergoing clinical testing. However, cardiovascular safety data remains limited. Beyond T cells, VISTA influences innate immune responses and shows maximum inhibitory activity in acidic environments, coinciding with key characteristics of acutely ischemic myocardium, highlighting the importance of evaluating cardiovascular safety.
Aim: To characterize myocardial VISTA expression in human heart failure and to evaluate the cardiovascular safety of VISTA inhibition in healthy mice and in a model of acute ischemic cardiac injury.
Methods: Myocardial tissue was obtained at heart transplantation from patients with ischemic and non-ischemic heart failure (screening: n = 7/group; validation: n = 80). Non-failing control myocardium (n = 6) was obtained from donors whose hearts were not transplanted for technical reasons. Co-inhibitory checkpoint expressions, including VISTA, were quantified by Western blot and correlated with clinical parameters. In vivo safety was assessed in aged C57BL/6 mice with anti-VISTA or isotype control for 4 weeks, and in an isoprenaline-induced injury model with treatment before, during, and after injury. Cardiac function was assessed by echocardiography, strain analysis, and ECG, and myocardial injury by histology.
Results: In failing myocardium, PD-L1 expression was increased while VISTA expression was uniformly reduced in both ischemic and non-ischemic heart failure. PD-L1 correlated with LVEF (r = −0.403, p = 0.002), whereas VISTA showed no association with LVEF (r = 0.016, p = 0.904), cardiac structure, or hemodynamic parameters. In healthy aged mice, VISTA inhibition did not alter cardiac structure or function (LVEF: 61.52 ± 10.04% vs. 61.14 ± 8.28%, p = 0.994). Following pharmacological ischemia, VISTA inhibition did not exacerbate injury or functional impairment, with no increase in infarct extent or inflammatory infiltration on histology.
Conclusion: Reduced myocardial VISTA expression in heart failure was not associated with cardiac dysfunction. VISTA inhibition did not induce adverse cardiac effects in healthy or acutely injured hearts in vivo. These findings support further clinical evaluation of VISTA as a next-generation immune checkpoint target.
Funding: Momentum Research Grant from the Hungarian Academy of Sciences (LP- 2021-38 to ZVV).