FGF-2 has been implicated in the cardiac response to hypertrophic stimuli. Angiotensin II (Ang II) contributes to maintain elevated blood pressure in hypertensive individuals and exerts direct trophic effects on cardiac cells. However, the role of FGF-2 in Ang II–induced cardiac hypertrophy has not been established. Therefore, mice deficient in FGF-2 expression were studied using a model of Ang II–dependent hypertension and cardiac hypertrophy. Echocardiographic measurements show the presence of dilated cardiomyopathy in normotensive mice lacking FGF-2. Moreover, hypertensive mice without FGF-2 developed no compensatory cardiac hypertrophy. In wild-type mice, hypertrophy was associated with a stimulation of the c-Jun N-terminal kinase, the extracellular signal regulated kinase, and the p38 kinase pathways. In contrast, mitogen-activated protein kinase (MAPK) activation was markedly attenuated in FGF-2–deficient mice. In vitro, FGF-2 of fibroblast origin was demonstrated to be essential in the paracrine stimulation of MAPK activation in cardiomyocytes. Indeed, fibroblasts lacking FGF-2 expression have a defective capacity for releasing growth factors to induce hypertrophic responses in cardiomyocytes. Therefore, these results identify the cardiac fibroblast population as a primary integrator of hypertrophic stimuli in the heart, and suggest that FGF-2 is a crucial mediator of cardiac hypertrophy via autocrine/paracrine actions on cardiac cells.
Corinne Pellieux, Alessandro Foletti, Giovanni Peduto, Jean-François Aubert, Jürg Nussberger, Friedrich Beermann, Hans-R. Brunner, Thierry Pedrazzini
Title and authors | Publication | Year |
---|---|---|
Serum fibroblast growth factor-2 levels complement vital biomarkers for diagnosing heart failure
Yu ZL, Cai ZH, Zheng JT, Jiang HY, Zhou YQ, Wong NK, Fu HB, Hong XB |
BMC Cardiovascular Disorders | 2024 |
FGFR4 Is Required for Concentric Growth of Cardiac Myocytes during Physiologic Cardiac Hypertrophy.
Campos I, Richter B, Thomas SM, Czaya B, Yanucil C, Kentrup D, Fajol A, Li Q, Secor SM, Faul C |
Journal of cardiovascular development and disease | 2024 |
Signaling Pathways and Potential Therapeutic Strategies in Cardiac Fibrosis
Bertaud A, Joshkon A, Heim X, Bachelier R, Bardin N, Leroyer AS, Blot-Chabaud M |
International journal of molecular sciences | 2023 |
Distinct mononuclear diploid cardiac subpopulation with minimal cell-cell communications persists in embryonic and adult mammalian heart.
Zhu M, Liang H, Zhang Z, Jiang H, Pu J, Hang X, Zhou Q, Xiang J, He X |
Frontiers of Medicine | 2023 |
The Microenvironment of the Pathogenesis of Cardiac Hypertrophy
Bazgir F, Nau J, Nakhaei-Rad S, Amin E, Wolf MJ, Saucerman JJ, Lorenz K, Ahmadian MR |
Cells | 2023 |
Fibroblast Growth Factor 2
Nickle A, Ko S, Merrill AE |
Differentiation; research in biological diversity | 2023 |
A Comprehensive Outlook on Dilated Cardiomyopathy (DCM): State-Of-The-Art Developments with Special Emphasis on OMICS-Based Approaches
Sarohi V, Srivastava S, Basak T |
Journal of Cardiovascular Development and Disease | 2022 |
Cardiac Hypertrophy: From Pathophysiological Mechanisms to Heart Failure Development
Caturano A, Vetrano E, Galiero R, Salvatore T, Docimo G, Epifani R, Alfano M, Sardu C, Marfella R, Rinaldi L, Sasso FC |
2022 | |
Autocrine Signaling in Cardiac Remodeling: A Rich Source of Therapeutic Targets
VF Segers, GW Keulenaer |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease | 2021 |
The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair
F Khosravi, N Ahmadvand, S Bellusci, H Sauer |
Frontiers in Cell and Developmental Biology | 2021 |
FGF/FGFR signaling in health and disease
Y Xie, N Su, J Yang, Q Tan, S Huang, M Jin, Z Ni, B Zhang, D Zhang, F Luo, H Chen, X Sun, JQ Feng, H Qi, L Chen |
Signal Transduction and Targeted Therapy | 2020 |
Resveratrol and Diabetic Cardiomyopathy: Focusing on the Protective Signaling Mechanisms
YJ Song, CB Zhong, W Wu |
Oxidative medicine and cellular longevity | 2020 |
Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation
Y Wang, F Yao, L Wang, Z Li, Z Ren, D Li, M Zhang, L Han, S Wang, B Zhou, L Wang |
Nature Communications | 2020 |
Acute Kidney Injury Sensitizes the Brain Vasculature to Ang II (Angiotensin II) Constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1)
L Zhao, X Cao, L Li, X Wang, Q Wang, S Jiang, C Tang, S Zhou, N Xu, Y Cui, W Hu, L Fei, Z Zheng, L Chen, MO Schmidt, Q Wei, J Zhao, R Labes, A Patzak, CS Wilcox, X Fu, A Wellstein, EY Lai |
Hypertension | 2020 |
Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology
SJ Forrester, GW Booz, CD Sigmund, TM Coffman, T Kawai, V Rizzo, R Scalia, S Eguchi |
Physiological reviews | 2018 |
Exploring the Clinical Relevance of Providing Increased Removal of Large Middle Molecules
M Wolley, M Jardine, CA Hutchison |
Clinical journal of the American Society of Nephrology : CJASN | 2018 |
Calcitriol downregulates fibroblast growth factor receptor 1 through histone deacetylase activation in HL-1 atrial myocytes
TW Lee, TI Lee, YK Lin, YH Kao, YJ Chen |
Journal of Biomedical Science | 2018 |
Telocinobufagin, a Novel Cardiotonic Steroid, Promotes Renal Fibrosis via Na+/K+-ATPase Profibrotic Signaling Pathways
D Kennedy, F Khalaf, B Sheehy, M Weber, B Agatisa-Boyle, J Conic, K Hauser, C Medert, K Westfall, P Bucur, O Fedorova, A Bagrov, W Tang |
International journal of molecular sciences | 2018 |
Physiologic, Pathologic, and Therapeutic Paracrine Modulation of Cardiac Excitation-Contraction Coupling
J Mayourian, DK Ceholski, DM Gonzalez, TJ Cashman, S Sahoo, RJ Hajjar, KD Costa |
Circulation research | 2018 |
Large uremic toxins: an unsolved problem in end-stage kidney disease
MJ Wolley, CA Hutchison |
Nephrology Dialysis Transplantation | 2018 |
Triggering Endogenous Cardiac Repair and Regeneration via Extracellular Vesicle-Mediated Communication
S Bollini, AM Smits, C Balbi, E Lazzarini, P Ameri |
Frontiers in physiology | 2018 |
Fibroblast Deletion of ROCK2 Attenuates Cardiac Hypertrophy, Fibrosis, and Diastolic Dysfunction
Toru Shimizu, Nikhil Narang, Phetcharat Chen, Brian Yu, Maura Knapp, Jyothi Janardanan, John Blair, James Liao |
JCI Insight | 2017 |
Densification of Type I Collagen Matrices as a Model for Cardiac Fibrosis
LJ Worke, JE Barthold, B Seelbinder, T Novak, RP Main, SL Harbin, CP Neu |
Advanced Healthcare Materials | 2017 |
Blood Pressure Control by a Secreted FGFBP1 (Fibroblast Growth Factor–Binding Protein)Novelty and Significance
E Tassi, EY Lai, L Li, G Solis, Y Chen, WE Kietzman, PE Ray, AT Riegel, WJ Welch, CS Wilcox, A Wellstein |
Hypertension | 2017 |
Multiple faces of fibroblast growth factor-23:
X Han, LD Quarles |
Current Opinion in Nephrology and Hypertension | 2016 |
Cardiac actions of fibroblast growth factor 23
C Faul |
Bone | 2016 |
The fibrosis-cell death axis in heart failure
A Piek, RA de Boer, HH Silljé |
Heart Failure Reviews | 2016 |
The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy
TM Mohamed, R Abou-Leisa, N Stafford, A Maqsood, M Zi, S Prehar, F Baudoin-Stanley, X Wang, L Neyses, EJ Cartwright, D Oceandy |
Nature Communications | 2016 |
Endothelial fibroblast growth factor receptor signaling is required for vascular remodeling following cardiac ischemia-reperfusion injury
SL House, AM Castro, TS Lupu, C Weinheimer, C Smith, A Kovacs, DM Ornitz |
American journal of physiology. Heart and circulatory physiology | 2016 |
Roles of FGF Signals in Heart Development, Health, and Disease
N Itoh, H Ohta, Y Nakayama, M Konishi |
Frontiers in Cell and Developmental Biology | 2016 |
Fibroblast growth factor 2 is an essential cardioprotective factor in a closed-chest model of cardiac ischemia-reperfusion injury
SL House, J Wang, AM Castro, C Weinheimer, A Kovacs, DM Ornitz |
Physiological Reports | 2015 |
Modulation of Cardiac Fibrosis by Kruppel-like Factor 6 through Transcriptional Control of Thrombospondin 4 in Cardiomyocytes
D Sawaki, L Hou, S Tomida, J Sun, H Zhan, K Aizawa, BK Son, T Kariya, E Takimoto, K Otsu, SJ Conway, I Manabe, I Komuro, SL Friedman, R Nagai, T Suzuki |
Cardiovascular Research | 2015 |
Protective and Therapeutic Effects of Chinese Medicine Formula Jiajian Yunvjian on Experimental Cardiac Remodeling after Myocardial Infarction Induced by Coronary Artery Ligation
J Du, W Gu, C Chen, Y Wang, J Lv |
Evidence-Based Complementary and Alternative Medicine | 2015 |
High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling
JJ Santiago, LJ McNaughton, N Koleini, X Ma, B Bestvater, BE Nickel, RR Fandrich, JT Wigle, DH Freed, RC Arora, E Kardami |
PloS one | 2014 |
Fibroblast growth factor receptor 1 signaling in adult cardiomyocytes increases contractility and results in a hypertrophic cardiomyopathy
SN Cilvik, JI Wang, KJ Lavine, K Uchida, A Castro, CM Gierasch, CJ Weinheimer, SL House, A Kovacs, CG Nichols, DM Ornitz |
PloS one | 2013 |
Pathophysiological roles of FGF signaling in the heart
N Itoh, H Ohta |
Frontiers in physiology | 2013 |
FGF2 modulates cardiac remodeling in an isoform- and sex-specific manner
E Nusayr, DT Sadideen, T Doetschman |
Physiological Reports | 2013 |
Cardiac development and physiology are modulated by FGF2 in an isoform- and sex-specific manner
E Nusayr, T Doetschman |
Physiological Reports | 2013 |
Fibroblast Growth Factor 2 Mediates Isoproterenol-induced Cardiac Hypertrophy through Activation of the Extracellular Regulated Kinase
SL House, BE House, B Glascock, T Kimball, E Nusayr, JE Schultz, T Doetschman |
Molecular and cellular pharmacology | 2011 |
Cellular Interplay between Cardiomyocytes and Nonmyocytes in Cardiac Remodeling
N Takeda, I Manabe |
International Journal of Inflammation | 2011 |
Changes in cardiac heparan sulfate proteoglycan expression and streptozotocin-induced diastolic dysfunction in rats
CM Strunz, M Matsuda, VM Salemi, A Nogueira, AP Mansur, IN Cestari, MV Marquezini |
Cardiovascular Diabetology | 2011 |
Intramyocardial fibroblast myocyte communication
R Kakkar, RT Lee |
Circulation research | 2010 |
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
Shared circuitry: developmental signaling cascades regulate both embryonic and adult coronary vasculature
KJ Lavine, DM Ornitz |
Circulation research | 2009 |
Biological functions of the low and high molecular weight protein isoforms of fibroblast growth factor-2 in cardiovascular development and disease
S Liao, J Bodmer, D Pietras, M Azhar, T Doetschman, JE Schultz |
Developmental Dynamics | 2008 |
Stemming heart failure with cardiac- or reprogrammed-stem cells
K Tateishi, N Takehara, H Matsubara, H Oh |
Journal of Cellular and Molecular Medicine | 2008 |
Myocardial gene expression of matched hibernating and control tissue from patients with ischemic left ventricular dysfunction
D Zohlnhöfer, TG Nührenberg, F Haas, F Bengel, A Schömig, PA Baeuerle, M Schwaiger |
Heart and Vessels | 2008 |
Paracrine effects of hypoxic fibroblast-derived factors on the MPT-ROS threshold and viability of adult rat cardiac myocytes
K Shivakumar, SJ Sollott, M Sangeetha, S Sapna, B Ziman, S Wang, EG Lakatta |
American journal of physiology. Heart and circulatory physiology | 2008 |
An improved protocol for primary culture of cardiomyocyte from neonatal mice
P Sreejit, S Kumar, RS Verma |
In vitro cellular & developmental biology. Animal | 2008 |
Fibroblast Growth Factor-2 Regulates Myocardial Infarct Repair
JA Virag, ML Rolle, J Reece, S Hardouin, EO Feigl, CE Murry |
The American Journal of Pathology | 2007 |
Pathways involved in the transition from hypertension to hypertrophy to heart failure. Treatment strategies
JW Wright, S Mizutani, JW Harding |
Heart Failure Reviews | 2007 |
Connexin43-dependent mechanism modulates renin secretion and hypertension
Jacques-Antoine Haefliger, Nathalie Krattinger, David Martin, Thierry Pedrazzini, Alessandro Capponi, Britta Doering, Achim Plum, Anne Charollais, Klaus Willecke, Paolo Meda |
Journal of Clinical Investigation | 2006 |
The fibroblast growth factor-2 controls the differentiation of resident cardiac precursors into functional cardiomyocytes
Nathalie Rosenblatt-Velin, Mario Lepore, Cristina Cartoni, Friedrich Beermann, Thierry Pedrazzini |
Journal of Clinical Investigation | 2005 |
Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation
P Pagliaro, C Penna |
Cardiovascular Drugs and Therapy | 2005 |
Angiotensin drives cardiac hypertrophy via transforming growth factor -beta 1
Michael Schneider |
Journal of Clinical Investigation | 2002 |