A novel modified physiologically relevant model for cardiac angiogenesis

• Published in: Microvascular research Vol. 114; pp. 84 - 91
• Main Authors: Zhang, Hao, Pan, Jiajun, Qiu, Fan, Wei, Tengteng, Li, Zhimin, Jiang, Xia, Zhuang, Wei, Liu, Zhiwei, Zhang, Zhongming, Dong, Hongyan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2017
• Subjects: Angiogenesis; Angiogenesis Inducing Agents - pharmacology; Angiogenesis Inhibitors - pharmacology; Animals; Animals, Newborn; Cardiac explants; Cell Hypoxia; Cellular Microenvironment; Collagen - metabolism; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Coronary Vessels - physiology; Drug Combinations; Fibronectin; Fibronectins - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - physiology; Humans; HUVECs; Laminin - metabolism; Matrigel; Neovascularization, Physiologic - drug effects; Proteoglycans - metabolism; Rats, Sprague-Dawley; Time Factors; Tissue Culture Techniques; Angiogenesis; Cardiac explants; Fibronectin; HUVECs; Matrigel
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1016/j.mvr.2017.06.007

Angiogenesis assays are important tools for studying both the mechanisms of cardiac angiogenesis and the potential development of therapeutic strategies to ischemic heart diseases. Currently, various assays have been used to quantitate cardiac tubule formation, yet no consensus has been reached regarding a suitable assay for evaluating the efficacy of angiogenic stimulants or inhibitors. Most in vivo angiogenesis assays are complex and difficult to interpret, whereas traditional in vitro angiogenesis models measure only one aspect of this process. To bridge the gap between in vivo and in vitro angiogenesis assays, here, we have developed a novel modified cardiac explants matrigel assay. We observed the morphology of vascular sprouts formed in three forms of cardiac angiogenesis assays then used quantitative image analyses to further compare the morphological features of vascular sprouts formed in two cardiac explants angiogenesis assays. Vascular sprouts formed in the fibronectin group were less and short, whereas those formed in the matrigel group were significantly longer, consisting of more area and branch points. Moreover, we found the benefits of this matrigel model by observing the ability of cardiac explants to form vascular sprouts under normoxia or hypoxia condition in the presence of angiogenic stimulant and inhibitor, VEGF and PEDF. In summary, the above analyses revealed that the morphology of vascular sprouts formed in this model appears more representative of myocardial capillary formation in vivo, and this accessible, reliable angiogenic assay is a more physiologically relevant assay which allows further assessment of pharmacologic compounds on cardiac angiogenesis. •Morphological observation of three cardiac angiogenesis assays•Cardiac explants matrigel assay acquires higher vascular sprout length and number.•Cardiac explants matrigel assay acquires higher branch point number and vascular sprout area.•Cardiac explants matrigel assay acquires higher tip cell and filopodia number.•Hypoxia promotes vascular sprout formation in cardiac explants matrigel assay.