PhD Scientific Days 2026

Poster Session 3.R - Cardiovascular Medicine and Research

Optimizing a drug screening platform to mimic iron-laden macrophages with pro-inflammatory phenotype

Előadó neve

Ms. Kovács, Andrea

Neptune code

LNELT8

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

06501100289

Előadó e-mail címe

kovacs.andrea3@semmelweis.hu

Az előadás címe

Optimizing a drug screening platform to mimic iron-laden macrophages with pro-inflammatory phenotype

Szerző(k) neve és munkahelye

Andrea Kovács¹, Zsófia Onódi¹, Sára Jezsoviczky¹, Artúr Tóth¹, Zoltán V. Varga¹

1: Department of Pharmacology and Pharmacotherapy

Bemutatás módja

Poszter

Szekció

Poster Session 3.R - Cardiovascular Medicine and Research

Language of the presentation

English

Preferred session

Cardiovascular Medicine and Research

Összefoglaló szövege

Cardiovascular diseases, such as ischemic heart disease or chronic heart failure (HF), are among the leading causes of death worldwide. Following cardiac injury, in the hemorrhagic microenvironment, recruited macrophages take up iron and mostly differentiate into a pro-inflammatory phenotype. Macrophages are crucial in maintaining iron homeostasis; but, in multiple aetiologies, the balance between their activation states tilts toward chronic inflammation. Anemia and iron deficiency are common among HF patients. We aim to establish a cell platform of iron-laden macrophages to investigate whether the currently approved HF medications have any effect on them. To model macrophages, we differentiated THP-1 human monocyte cells with 100 ng/mL PMA, then primed the M0 macrophages toward a pro-inflammatory phenotype with 100 ng/mL LPS. To simulate iron-overload, we tested freshly isolated red blood cells (RBC), senescent RBCs, or 200 µM ferric ammonium citrate (FAC) supplementation for 6 hours. Then, to induce NLRP3 inflammasome activation, we added nigericin for 20 minutes to the FBS-free media. We conducted qRT-PCR analysis on our samples to assess major changes in macrophage phenotype and iron homeostasis.
Our preliminary findings showed that RBCs induced a significant elevation of Cxcl10 (an M1 macrophage marker) expression in all conditions. Senescent RBC treatment induced significant Nlrp3 expression in the pro-inflammatory macrophages. Interestingly, Hmox1 showed the most prominent elevation by FAC treatment. Transferrin-dependent iron uptake was significantly higher in the RBC and LPS-treated group. However, iron export via ferroportin was elevated in all treatment groups, indicating that the 6-hour treatment might not be sufficient to induce iron-overload. The marked elevations in Ncoa4 (a ferritinophagy marker) by RBC and senescent RBC treatment suggest that iron is accumulating in the labile iron pool (LIP), which is a step toward iron-overload and might sensitize cells toward ferroptosis.
We developed an inflammatory, iron-laden phenotype, but our model needs further optimization. Iron-laden macrophages might prove to be an important drug target in the future. The expression change in Ncoa4 is in line with previous observations that it might have a detrimental role indicating elevated ferritinophagy in heart failure.
Funding: 152247; NKFIH , SE250+

University

Semmelweis University

Supervisor

Zsófia Gulyás-Onódi

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 before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4674

Start

14:30

End

14:33