Abstract
Endothelial cells form the inner lining of blood vessels, in a process known as angiogenesis. Excessive angiogenesis is a hallmark of several diseases, including cancer. The number of studies in endothelial cell metabolism has increased in recent years, and new metabolic targets for pharmacological treatment of pathological angiogenesis are being proposed. In this work, we wanted to address experimental evidence of substrate (namely glucose, glutamine and palmitate) dependence in immortalized dermal microvascular endothelial cells in comparison to primary endothelial cells. In addition, due to the lack of information about lactate metabolism in this specific type of endothelial cells, we also checked their capability of utilizing extracellular lactate. For fulfilling these aims, proliferation, migration, Seahorse, substrate uptake/utilization, and mRNA/protein expression experiments were performed. Our results show a high glycolytic capacity of immortalized dermal microvascular endothelial cells, but an early independence of glucose for cell growth, whereas a total dependence of glutamine to proliferate was found. Additionally, in contrast with reported data in other endothelial cell lines, these cells lack monocarboxylate transporter 1 for extracellular lactate incorporation. Therefore, our results point to the change of certain metabolic features depending on the endothelial cell line.
Highlights
Angiogenesis is the process of formation of new blood vessels from the pre-existing vascular bed [1]
human dermal microvascular ECs (HMEC) were able to grow in the absence of glucose for the first three days at the same rate as cells grown with both glucose and glutamine (Figure 1b)
HMEC did not grow under glutamine starvation even in the presence of glucose (p < 0.05) (Figure 1b)
Summary
Angiogenesis is the process of formation of new blood vessels from the pre-existing vascular bed [1]. Excessive pathological angiogenesis has been described in some diseases such as diabetes mellitus, rheumatoid arthritis, several retinopathies, and cancer [2]. Targeting angiogenesis emerged as a potential therapy for these diseases alone or in combination with other pharmacological targets, either by the use of multitargeted drugs or through the combination of several drugs targeting different pathways involved in the angiogenic process [3,4]. The study of endothelial cell (EC) metabolism has grown in importance since the discovery that a glycolytic enzyme, phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3), is essential for vessel sprouting [5]. Glutamine was seen to be essential for the angiogenic switch as well [6]. Inhibition of fatty acid metabolism, carnitine palmitoyltransferase 1a (CPT1a), was shown to disrupt
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