Mechanical load induced by glass microspheres releases angiogenic factors from neonatal rat ventricular myocytes cultures and causes arrhythmias
| Autor: | Asaf Danon, M. Silberman, Yotam Reisner, Jutta Schaper, Ofer Binah, D. Y. Barac, Mark Shilkrut, Sawa Kostin, Moshe Shoham, O. Salomon, Naama Zeevi-Levin |
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| Rok vydání: | 2008 |
| Předmět: |
ventricular myocytes
action potential propagation mechanical load Angiogenesis Heart Ventricles Basic fibroblast growth factor Guidelines as Topic Culture Media Serum-Free Afterdepolarization chemistry.chemical_compound intracellular calcium transients Coated Materials Biocompatible Myocyte Animals Myocytes Cardiac Cells Cultured Tube formation cyclic stretch Arrhythmias Cardiac Cell Biology Anatomy Equipment Design Articles Immunohistochemistry Microspheres Rats Glass microsphere Endothelial stem cell Vascular endothelial growth factor chemistry Animals Newborn Connexin 43 Biophysics Molecular Medicine Angiogenesis Inducing Agents glass microspheres Collagen Glass Stress Mechanical hypertrophy arrhythmias |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| Popis: | In the present study, we tested the hypothesis that similar to other mechanical loads, notably cyclic stretch (simulating pre-load), glass microspheres simulating afterload will stimulate the secretion of angiogenic factors. Hence, we employed glass microspheres (average diameter 15.7 microm, average mass 5.2 ng) as a new method for imposing mechanical load on neonatal rat ventricular myocytes (NRVM) in culture. The collagen-coated microspheres were spread over the cultures at an estimated density of 3000 microspheres/mm2, they adhered strongly to the myocytes, and acted as small weights carried by the cells during their contraction. NRVM were exposed to either glass microspheres or to cyclic stretch, and several key angiogenic factors were measured by RT-PCR. The major findings were: (1) In contrast to other mechanical loads, such as cyclic stretch, microspheres (at 24 hrs) did not cause hypertrophy. (2) Further, in contrast to cyclic stretch, glass microspheres did not affect Cx43 expression, or the conduction velocity measured by means of the Micro-Electrode-Array system. (3) At 24 hrs, glass microspheres caused arrhythmias, probably resulting from early afterdepolarizations. (4) Glass microspheres caused the release of angiogenic factors as indicated by an increase in mRNA levels of vascular endothelial growth factor (80%), angiopoietin-2 (60%), transforming growth factor-beta (40%) and basic fibroblast growth factor (15%); these effects were comparable to those of cyclic stretch. (5) As compared with control cultures, conditioned media from cultures exposed to microspheres increased endothelial cell migration by 15% (P0.05) and endothelial cell tube formation by 120% (P0.05), both common assays for angiogenesis. In conclusion, based on these findings we propose that loading cardiomyocytes with glass microspheres may serve as a new in vitro model for investigating the role of mechanical forces in angiogenesis and arrhythmias. |
| Databáze: | OpenAIRE |
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