Non-neuronal nicotinic alpha 7 receptor, a new endothelial target for revascularization.
Alpha 7 nicotinic acetylcholine receptor (alpha7 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 alpha7 nAChR is involved in angiogenesis. Here, we investigated the feasibility of alpha7 nAChR for revascularization in ischemic heart disease. RT-PCR and immunohistochemistry were used to examine the expression of alpha7 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 alpha7 nAChR agonists choline increased the expression of alpha7 nAChR mRNA and protein, the intracellular Ca 2+ concentration, proliferation and tube formation of ECs. Reverse effects were observed by using alpha7 nAChR antagonist alpha-BTX. Furthermore, in the rat model of MI, alpha7 nAChR agonist enhanced the capillary density in ischemic tissues, whereas antagonist mecamylamine and alpha-BTX inhibited the effect. Our results suggest that alpha7 nAChR is involved in the regulation of cellular function in ECs, and capillary formation in MI, which are the important steps of angiogenesis. Therefore, alpha7 nAChR on ECs may be a new endothelium target for revascularization in therapeutic angiogenesis of ischemic heart disease.
Li
Xiao-Wei
XW
Department of Cardiovascular Pharmacology, Institute of Pharmacology and Toxicology, 27 Tai Ping Road, Beijing 100850, China.
Wang
Hai
H
D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D008464:Mecamylamine; D002118:Calcium