ROLE OF FOLLISTATIN LIKE 1 (FSTL1) PROTEIN IN RECENT ONSET DILATED CARDIOMYOPATHY: ENERGETIC METABOLISM PERSPECTIVE
Topic: Heart failure | |
| Type: Poster - doctors , Number in the programme: 43 | |
| Novák J.1, Hořák M.2, Fialová Kučerová J.3, Poloczková H.4, Kučera J.3, Uldrijan S.5, Rotrekl V.5, Bienertová Vašků J.3, Krejčí J.4 1 II. interní klinika, Fakultní Nemocnice u svaté Anny v Brně a Lékařská Fakulta Masarykovy univerzity, Brno, 2 Department of Physiology, Masaryk Univeristy, Brno, 3 Department of Physiology, Masaryk University, Brno, 4 1st Department of Cardio-Angiology, St. Anne's University Hospital in Brno, Brno, 5 Department of Biology, Masaryk Univeristy, Brno | |
Aim: Follistatin-like 1 (FSTL1) protein is a cardiokine involed in heart failure pathophysiology. In our previous study, we have shown that changes in its plasmatic levels predict left-ventricular function recovery in recent onset dilated cardiomyopathy (RODCM) patients. In the current study we aimed to better describe its role in cardiomyocytes energetic metabolism to further explain our observations. Methods: CCTL14 (human embryonic stem cells) cell line was used. FSTL1 knockdown was induced by transfection with lentiviral vector plasmids. Levels and distribution of proteins involved energetic metabolism were studied using western blot and immunocytochemistry. Involvement of FSTL1 in energetic/mitochondrial metabolism was analyzed using the ATP luminescence assay, mitochondrial membrane potential (MMP) measurement (using tetramethyl rhodamine methyl ester fluorescent dye), and mitochondrial oxygen consumption rate (OCR) using Seahorse XFp analyzer. Results: We show that FSTL1 knock-down negatively affects oxidative phosphorylation of several proteins leading to decrease in ATP production in CCTL14 cells under normoxia. Decrease in FSTL1 further decreased MMP in CCTL14 cells, and decreased both basal (55.05 ± 3.35 vs. 33.70 ± 2.07 pmol/min/cells (p = 0.003)), and maximal (78.53 ± 6.59 vs. 47.35 ± 2.82 pmol/min/cells (p = 0.006)) OCR compared to controls. Conclusion: We have shown that FSTL1 affects mitochondrial/energetic metabolism by altering MMP, OCR and ATP production in cardiomyocytes in vitro. Supported by NU22-02-00418 and LX22NPO5104 projects. | |
