Sustained β-AR stimulation induces synthesis and secretion of growth factors in cardiac myocytes that affect on cardiac fibroblast activation
Autor: | Primchanien Moongkarndi, Warisara Parichatikanond, Narawat Nuamnaichati, Supachoke Mangmool, Vilasinee Hirunpanich Sato |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A medicine.medical_specialty Cardiac fibrosis medicine.medical_treatment Adrenergic beta-Antagonists Primary Cell Culture Biology General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley 03 medical and health sciences Paracrine signalling Internal medicine Receptors Adrenergic beta medicine Myocyte Animals Myocytes Cardiac General Pharmacology Toxicology and Pharmaceutics Cell Proliferation Growth factor Myocardium Cardiac myocyte Isoproterenol Cell Differentiation Heart General Medicine Fibroblasts medicine.disease Cyclic AMP-Dependent Protein Kinases Rats CTGF 030104 developmental biology Endocrinology Animals Newborn Cytokines Intercellular Signaling Peptides and Proteins Myocardial fibrosis Receptors Adrenergic beta-2 Myofibroblast Signal Transduction |
Zdroj: | Life sciences. 193 |
ISSN: | 1879-0631 |
Popis: | Paracrine factors, including growth factors and cytokines, released from cardiac myocytes following β-adrenergic receptor (β-AR) stimulation regulate cardiac fibroblasts. Activated cardiac fibroblasts have the ability to increase collagen synthesis, cell proliferation and myofibroblast differentiation, leading to cardiac fibrosis. However, it is unknown which β-AR subtypes and signaling pathways mediate the upregulation of paracrine factors in cardiac myocytes. In this study, we demonstrated that sustained stimulation of β-ARs significantly induced synthesis and secretion of growth factors, including connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF), via the cAMP-dependent and protein kinase A (PKA)-dependent pathways. In addition, isoproterenol (ISO)-mediated synthesis and secretion of CTGF and VEGF through the β1-AR and β2-AR subtypes. Paracrine factors released by cardiac myocytes following sustained β-AR stimulation are necessary for the induction of cell proliferation and synthesis of collagen I, collagen III and α-smooth muscle actin (α-SMA) in cardiac fibroblasts, confirming that β-AR overstimulation of cardiac myocytes induces cardiac fibrosis by releasing several paracrine factors. These effects can be antagonized by β-blockers, including atenolol, metoprolol, and propranolol. Thus, the use of β-blockers may have beneficial effects on the treatment of myocardial fibrosis in patients with heart failure. |
Databáze: | OpenAIRE |
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