Non-neuronal nicotinic alpha 7 receptor, a new endothelial target for revascularization

Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) is widely expressed in the central and peripheral nervous systems, and is also found in several non-neuronal tissues, such as endothelial cells (ECs), bronchial epithelial cells, skin keratinocytes and vascular smooth muscle cells. Recent evidence suggests that α7 nAChR is involved in angiogenesis. Here, we investigated the feasibility of α7 nAChR for revascularization in ischemic heart disease. RT-PCR and immunohistochemistry were used to examine the expression of α7 nAChR in human umbilical vein endothelial cell (HUVECs). The cellular function was examined using MTT, fluorescence confocal microscopy and angiogenesis assay in vitro. The capillary density in the rat model of myocardial infarction (MI) was investigated using immunohistochemistry. The results showed that α7 nAChR agonists choline increased the expression of α7 nAChR mRNA and protein, the intracellular Ca 2+ concentration, proliferation and tube formation of ECs. Reverse effects were observed by using α7 nAChR antagonist α-BTX. Furthermore, in the rat model of MI, α7 nAChR agonist enhanced the capillary density in ischemic tissues, whereas antagonist mecamylamine and α-BTX inhibited the effect. Our results suggest that α7 nAChR is involved in the regulation of cellular function in ECs, and capillary formation in MI, which are the important steps of angiogenesis. Therefore, α7 nAChR on ECs may be a new endothelium target for revascularization in therapeutic angiogenesis of ischemic heart disease.