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Fang Wen,1,* Shantong Jiang,1– 4,* Ping Yuan,1– 5,* Jinbo Liu,1– 4 Xiu Bai,1 Hongwei Zhao,1– 4,6,7 Xin Chen,1– 4,7 Yan-Bing Gong,5 Roland Asmar,8 Hongyu Wang1– 4,6,7 1Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, People’s Republic of China; 2Vascular Health Research Center of Peking University Health Science Center (VHRC-PKUHSC), Beijing, People’s Republic of China; 3Beijing Shijingshan District Key Clinical Specialty of Vascular Medicine, Beijing, People’s Republic of China; 4Heart and Vascular Health Research Center of Peking University Clinical Research Institute (HVHRC-PUCRI), Beijing, People’s Republic of China; 5Department of Scientific Research, Peking University Shougang Hospital, Beijing, People’s Republic of China; 6State Key Laboratory of Vascular Homeostasis and Remodeling, (Peking University), Beijing, People’s Republic of China; 7Heart and Vascular Health Research Center of Chengdu Medical College (HVHRC-CMC), Chengdu, People’s Republic of China; 8Foundation-Medical Research Institutes, Beirut, Lebanon*These authors contributed equally to this workCorrespondence: Hongyu Wang, Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, 100144, People’s Republic of China, Email dr.hongyuwang@foxmail.comAbstract: Cardiovascular disease(CVD) has become a major disease burden affecting people’s health in China. Blood vessels are very important for human health and are the “sentinel” for the development of many cardiovascular and cerebrovascular diseases. The key to effectively preventing fatal, disabling heart, brain and peripheral vascular events lies in controlling traditional and non-traditional risk factors for vascular health from the source, and early assessment and intervention of early vascular lesions. Since 2004, China government promoted the early detection technology of vascular lesions and vascular medicine, and proposed the Bei

Conotoxins are a pool of disulfide-rich peptide neurotoxins produced by cone snails for predation and defense. They are a rich reservoir of novel ligands for ion channels, neurotransmitter receptors and transporters in the nervous system. In this study, we identified a novel conotoxin component, O-conotoxin GeXXVIIA, from the venom of Conus generalis. The native form of this component is a disulfide-linked homodimer of a 5-Cys-containing peptide. Surprisingly, our electrophysiological studies showed that, in comparison to the folded monomers, the linear peptide of this toxin had the highest inhibitory activity at the human α9α10 nicotinic acetylcholine receptor (nAChR), with an IC50 of 16.2 ± 1.4 nM. The activities of the N-terminal and C-terminal halves of the linear toxin are markedly reduced compared with the full-length toxin, suggesting that the intact sequence is required to potently inhibit the hα9α10 nAChR. α9α10 nAChRs are expressed not only in the nervous system, but also in a variety of non-neuronal cells, such as cochlear hair cells, keratinocytes, epithelial and immune cells. A potent inhibitor of human α9α10 nAChRs, such as GeXXVIIA, would facilitate unraveling the functions of this nAChR subtype. Furthermore, this unusual nAChR inhibitor may lead to the development of novel α9α10 nAChR-targeting drugs.