PhD Scientific Days 2026
Budapest, 16-18 June 2026
Cardiovascular Medicine and Research 3.
Loss of ICOSL Signaling Promotes Myocardial Matrix Stiffening and Functional Decline
Előadó neve
Hegedűs, Zsombor, MSc
Neptune code
RVZY24
Előadó munkahelye
Department of Pharmacology and Pharmacotherapy, Semmelweis University
Előadó telefonszáma
06202609682
Előadó e-mail címe
hegedus.zsombor@semmelweis.hu
Az előadás címe
Loss of ICOSL Signaling Promotes Myocardial Matrix Stiffening and Functional Decline
Szerző(k) neve és munkahelye
Zsombor I. Hegedűs1,2,3, Márk E. Jakab1,2,3, Szabolcs Farkas1,2, Anna Kulin1,2,3, Péter Ferdinandy1,2,4,5, Zoltán V. Varga1,2,3
1: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2: Center for Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary
3: MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary
4: Pharmahungary Group, Szeged, Hungary
5: MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
Bemutatás módja
Szóbeli
Szekció
Cardiovascular Medicine and Research 3.
Language of the presentation
English
Preferred session
Cardiovascular Medicine and Research
Összefoglaló szövege
Introduction: Cardiac fibroblasts are central to myocardial repair; however, excessive activation promotes maladaptive fibrosis and heart failure. The Inducible T-cell Co-stimulator (ICOS) and its Ligand (ICOSL) have emerging roles beyond adaptive immunity, but their involvement in cardiac remodeling remains poorly defined.
Aims: To investigate the role of ICOS-ICOSL signaling in cardiac remodeling and fibrosis using a murine model of angiotensin II (Ang-II)-induced cardiac injury.
Methods: Mice received Ang-II (1.5 mg/kg/day) or saline for 15 days. ICOS/ICOSL signaling was inhibited using monoclonal antibodies (150 µg i.p., every 3 days). Cardiac function was assessed by echocardiography, and remodeling by histology, RNAscope, and qPCR.
Results: In Ang-II-infused mice, blockade of ICOS or ICOSL significantly increased mortality (40-50%), compared with Ang-II alone (13%). Both treatments exacerbated systolic dysfunction, reducing ejection fraction (EF). ICOSL inhibition further aggravated remodeling, increasing relative wall thickness (RWT) and left ventricular remodeling index (LVRI). Myocardial fibrosis was enhanced by ICOSL blockade, with elevated Ctgf, Tgfb1, and Col1a1 expression and an increased Col1a1/Col3a1 ratio, whereas ICOS inhibition increased Col3a1 expression. These findings were corroborated by COL1A1 and fibroblast activation protein (FAP) immunohistochemistry. Co-expression of Icosl and Col1a1 increased in fibrotic myocardium but not in perivascular regions. The reduction in the Myh6/Myh7 ratio was attenuated by ICOS blockade but exacerbated by ICOSL inhibition. Nppb expression and circulating NT-proBNP levels were normalized by ICOS inhibition but remained elevated following ICOSL blockade.
Conclusions: ICOS-ICOSL signaling modulates the cardiac stress response. While ICOS inhibition exerts a modest effect on hypertrophy and fibrosis, ICOSL blockade accelerates adverse remodeling, matrix stiffening, and functional decline. These findings identify ICOSL-driven signaling as a regulator of fibrotic pathology and highlight the potential risk of therapeutically targeting this pathway.
Funding: Supported by Project RRF-2.3.1-21-2022-00003 (European Union), Semmelweis Lendület Program 2024, Semmelweis 250+ Excellence Fellowship, and the 2025-2.1.1-EKÖP-2025-00014 University Research Scholarship Programme (Ministry for Culture and Innovation).
University
Semmelweis University
Supervisor
Zoltán V. Varga
Publication of my abstract
I do not give consent to the publication of my abstract on the website of the congress.
phd.section.field
in doctoral studies after complex exam (PhD)
Kind
Szabad
Status
elfogadva
Accepted presentation method
szóbeli
Előadás fájl jóváhagyás
nem hagyta jóvá
Előadó
8937
Start
16:15
End
16:25