Inhibition of Notch rescues the angiogenic potential impaired by cardiovascular risk factors in epicardial adipose stem cells
| Autor: | Raquel Ferrer-Lorente, Lina Badimon, Maria Teresa Bejar, Esther Peña |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Angiogenesis Adipose tissue Biochemistry angiogenesis 03 medical and health sciences Downregulation and upregulation In vivo Risk Factors Internal medicine ZDF Genetics medicine Diabetes Mellitus Animals Myocytes Cardiac Obesity Molecular Biology Matrigel Neovascularization Pathologic Receptors Notch business.industry Stem Cells differentiation epicardial adipose tissue Hes/Hey family Rats Rats Zucker Up-Regulation 030104 developmental biology Endocrinology Adipose Tissue Gene Expression Regulation Adipogenesis Cardiovascular Diseases Stem cell business Homeostasis Biotechnology |
| Zdroj: | FASEB JOURNAL r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | The epicardial adipose tissue (EAT) is a reservoir of adipose-derived stem cells (ASCs), with as yet unknown effects on myocardial and coronary arteries homeostasis. The purpose of this study was to investigate the angiogenic function of epicardial ASCs and their regulation by the common cardiovascular risk factors (CVRFs) affecting heart disease. Epicardial fat was obtained from a rodent model with clustering of CVRFs [Zucker diabetic fatty (ZDF)-Lepr(fa)] rats and from their lean control (ZDF-Crl) littermates without CVRFs, ASCs were isolated, and their function was assessed by proliferation and differentiation assays, flow cytometry, gene expression, and in vivo Matrigel angiogenesis analysis. Epicardial ASCs from both groups showed adipogenic and osteogenic differentiation capacity; however, epicardial ASCs from CVRF animals had a lesser ability to form tubular structures in vitro after endothelial differentiation, as well as a reduced angiogenic potential in vivo compared to control animals. Epicardial ASCs from CVRF rats showed up-regulation of the downstream Notch signaling genes Hes7, Hey1, and Heyl compared with control animals. The inhibition of Notch signaling by conditioning epicardial ASCs from CVRF animals with a γ-secretase inhibitor induced a reduction in Hes/Hey gene expression and rescued their angiogenic function in vivo We report for the first time the impact of CVRF burden on the ASCs of EAT and that the defective function is in part caused by increased Notch signaling. Conditioning ASCs by blocking Notch signaling rescues their angiogenic potential.-Bejar, M. T., Ferrer-Lorente, R., Peña, E., Badimon, L. Inhibition of Notch rescues the angiogenic potential impaired by cardiovascular risk factors in epicardial adipose stem cells. |
| Databáze: | OpenAIRE |
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