TY - JOUR
T1 - Cardiac FGF23
T2 - new insights into the role and function of FGF23 after acute myocardial infarction
AU - Schumacher, David
AU - Alampour-Rajabi, Setareh
AU - Ponomariov, Victor
AU - Curaj, Adelina
AU - Wu, Zhuojun
AU - Staudt, Mareike
AU - Rusu, Mihaela
AU - Jankowski, Vera
AU - Marx, Nikolaus
AU - Jankowski, Joachim
AU - Brandenburg, Vincent
AU - Liehn, Elisa A.
AU - Schuh, Alexander
N1 - Funding Information:
Sources of Founding: The study was supported by the Interdisciplinary Center for Clinical Research (IZKF) Aachen (Junior Research Group E.A.L). David Schumacher was supported by the Deutsch Herzstiftung (Kaldenbach-Doktorandenstipendium). Vera Jankowski and Joachim Jankowski are supported by the German Research Foundation (DFG) with the SFB/TRR219 (Subprojects C-04, S-03).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019
Y1 - 2019
N2 - Objective: We aimed to elucidate the local role of FGF23 after myocardial infarction in a mouse model induced by left anterior descending artery (LAD) ligation.Approach and results: (C57BL/6N) mice underwent MI via LAD ligation and were sacrificed at different time-points post MI. The expression and influence of FGF23 on fibroblast and macrophages was also analyzed using isolated murine cells.We identified enhanced cardiac FGF23 mRNA expression in a time-dependent manner with an early increase, already on the first day after MI. FGF23 protein expression was abundantly detected in the infarcted area during the inflammatory phase. While described to be primarily produced in bone or macrophages, we identified cardiac fibroblasts as the only source of local FGF23 production after MI. Inflammatory mediators, such as IL-1 beta, IL-6 and TNF-alpha, were able to induce FGF23 expression in these cardiac fibroblasts. Interestingly, we were not able to detect FGF23 at later time points after MI in mature scar tissue or remote myocardium, most likely due to TGF-beta 1, which we have shown to inhibit the expression of FGF23. We identified FGFR1c to be the most abundant receptor for FGF23 in infarcted myocardium and cardiac macrophages and fibroblasts. FGF23 increased migration of cardiac fibroblast, as well as expression of Collagen 1, Periostin, Fibronectin and MMP8. FGF23 also increased expression of TGF-beta 1 in M2 polarized macrophages.Conclusion: In conclusion, cardiac fibroblasts in the infarcted myocardium produce and express FGF23 as well as its respective receptors in a time-dependent manner, thus potentially influencing resident cell migration. The transitory local expression of FGF23 after MI points towards a complex role of FGF23 in myocardial ischemia and warrants further exploration, considering its role in ventricular remodeling. (C) 2019 Elsevier Inc. All rights reserved.
AB - Objective: We aimed to elucidate the local role of FGF23 after myocardial infarction in a mouse model induced by left anterior descending artery (LAD) ligation.Approach and results: (C57BL/6N) mice underwent MI via LAD ligation and were sacrificed at different time-points post MI. The expression and influence of FGF23 on fibroblast and macrophages was also analyzed using isolated murine cells.We identified enhanced cardiac FGF23 mRNA expression in a time-dependent manner with an early increase, already on the first day after MI. FGF23 protein expression was abundantly detected in the infarcted area during the inflammatory phase. While described to be primarily produced in bone or macrophages, we identified cardiac fibroblasts as the only source of local FGF23 production after MI. Inflammatory mediators, such as IL-1 beta, IL-6 and TNF-alpha, were able to induce FGF23 expression in these cardiac fibroblasts. Interestingly, we were not able to detect FGF23 at later time points after MI in mature scar tissue or remote myocardium, most likely due to TGF-beta 1, which we have shown to inhibit the expression of FGF23. We identified FGFR1c to be the most abundant receptor for FGF23 in infarcted myocardium and cardiac macrophages and fibroblasts. FGF23 increased migration of cardiac fibroblast, as well as expression of Collagen 1, Periostin, Fibronectin and MMP8. FGF23 also increased expression of TGF-beta 1 in M2 polarized macrophages.Conclusion: In conclusion, cardiac fibroblasts in the infarcted myocardium produce and express FGF23 as well as its respective receptors in a time-dependent manner, thus potentially influencing resident cell migration. The transitory local expression of FGF23 after MI points towards a complex role of FGF23 in myocardial ischemia and warrants further exploration, considering its role in ventricular remodeling. (C) 2019 Elsevier Inc. All rights reserved.
KW - FGF23
KW - Cardiac fibroblast
KW - Macrophages
KW - Cytokines
KW - Myocardial infarction
KW - Inflammation
KW - FIBROBLAST-GROWTH-FACTOR
KW - LEFT-VENTRICULAR HYPERTROPHY
KW - CARDIOVASCULAR EVENTS
KW - HEART-FAILURE
KW - VITAMIN-D
KW - FGF-23
KW - MORTALITY
KW - EXPRESSION
KW - DISEASE
KW - FACTOR-23
U2 - 10.1016/j.carpath.2019.02.001
DO - 10.1016/j.carpath.2019.02.001
M3 - Article
C2 - 30852297
SN - 1054-8807
VL - 40
SP - 47
EP - 54
JO - Cardiovascular Pathology
JF - Cardiovascular Pathology
ER -