Effects of Dual Purinoceptor-dependent Approach on Release of Vascular Endothelial Growth Factor From Human Microvascular Endothelial Cell (HMEC-1) and Endothelial Cell Condition

In the recent years, the awareness of the role purinergic signaling plays as a therapeutic target has increased considerably. The purinoceptor allows the action of extracellular nucleotides (P2 receptors) and intermediary products of their metabolism, such as adenosine (P1 receptors), regulating pivotal processes occurring in the cardiovascular system. This study focuses on a dual purinoreceptor-dependent approach, based on the activation of adenosine P1 receptors with the simultaneous inhibition of P2Y12 receptors that can be used as novel platelet inhibitors in antithrombotic therapy. Endothelial cells are directly exposed to the drugs circulating in the bloodstream. That is why effects of our concept on human microvascular endothelial cells (HMEC-1) were examined in in vitro studies, such as enzyme-linked immunosorbent assay and scratch assays. In response to adenosine receptor agonists, levels of secreted vascular endothelial growth factor varied. Two of them, 5 '-N-ethylcarboxamidoadenosine and MRE0094 remarkably increased vascular endothelial growth factor release. The elevated levels were reduced when used together with the P2Y12 receptor antagonist. Also, rates of wound closure in a scratch assay were significantly reduced in these cases. The results suggest that the proposed treatment does not impair endothelial cell condition. In addition, it is suggested as a collateral benefit, namely solving the problem of excessive activation of endothelial cells during antiplatelet therapy.