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Angiopoietins are important growth factors for vascular development and quiescence. They are promising targets for pro- or anti-angiogenic therapies in diverse pathologies, but the mechanisms of the ANGPT/TIE2 system are complex and not well understood. In the present study, the separate and combined effects of angiopoietin 1 and angiopoietin 2 were studied, using a recently developed in vitro angiogenesis model that allows both a quantitative and qualitative evaluation of the angiogenic cascade. This cell culture model was performed with microvascular endothelial cells (ECs) originating from different vascular beds, i.e. dermal ECs and cardiac ECs. In addition, the expression of the angiopoietins and the receptors, TIE1 and TIE2 was analyzed with RT-qPCR. This study revealed that the angiopoietins provoked a differential response in the two endothelial cultures. Both angiopoietin 1 as well as angiopoietin 2 elicited an angiogenic cascade in the dermal ECs but not in the cardiac ECs. In addition, the RT-qPCR data revealed marked differences in the endogenous expression pattern of these factors, indicating that the origin of endothelial cells might have an important impact on their angiogenic potential.