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
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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