A novel modified physiologically relevant model for cardiac angiogenesis

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.