Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions
| Autor: | Abdul Q. Sheikh, Robert B. Hinton, Wei Huang, Jennifer R. Hurley, Courtney Kuesel, Toloo Taghian, Daria A. Narmoneva, Yigang Wang |
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| Rok vydání: | 2014 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Physiology Angiogenesis Cardiomyopathy Neovascularization Physiologic Apoptosis Nitric Oxide Diabetes Mellitus Experimental Fibrosis Internal medicine Diabetes mellitus medicine Animals Endothelial dysfunction Cells Cultured Cell Proliferation business.industry Endothelial Cells Articles Cell Biology medicine.disease Coronary Vessels Biomechanical Phenomena Culture Media Rats Vascular endothelial growth factor B Endothelial stem cell Vascular endothelial growth factor A Endocrinology Cancer research Endothelium Vascular business |
| Zdroj: | American Journal of Physiology-Cell Physiology. 306:C768-C778 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00201.2013 |
| Popis: | Diabetes-induced cardiomyopathy is characterized by cardiac remodeling, fibrosis, and endothelial dysfunction, with no treatment options currently available. Hyperglycemic memory by endothelial cells may play the key role in microvascular complications in diabetes, providing a potential target for therapeutic approaches. This study tested the hypothesis that a proangiogenic environment can augment diabetes-induced deficiencies in endothelial cell angiogenic and biomechanical responses. Endothelial responses were quantified for two models of diabetic conditions: 1) an in vitro acute and chronic hyperglycemia where normal cardiac endothelial cells were exposed to high-glucose media, and 2) an in vivo chronic diabetes model where the cells were isolated from rats with type I streptozotocin-induced diabetes. Capillary morphogenesis, VEGF and nitric oxide expression, cell morphology, orientation, proliferation, and apoptosis were determined for cells cultured on Matrigel or proangiogenic nanofiber hydrogel. The effects of biomechanical stimulation were assessed following cell exposure to uniaxial strain. The results demonstrate that diabetes alters cardiac endothelium angiogenic response, with differential effects of acute and chronic exposure to high-glucose conditions, consistent with the concept that endothelial cells may have a long-term “hyperglycemic memory” of the physiological environment in the body. Furthermore, endothelial cell exposure to strain significantly diminishes their angiogenic potential following strain application. Both diabetes and strain-associated deficiencies can be augmented in the proangiogenic nanofiber microenvironment. These findings may contribute to the development of novel approaches to reverse hyperglycemic memory of endothelium and enhance vascularization of the diabetic heart, where improved angiogenic and biomechanical responses can be the key factor to successful therapy. |
| Databáze: | OpenAIRE |
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