title: Rutaecarpine prevented dysfunction of endothelial gap junction induced by Ox-LDL via activation of TRPV1.
abstract: Gap junctions, which is formed by connexins, has been proved to play an important role in the atherogenesis development. Rutaecarpine was reported to inhibited monocyte migration, which indicates its potential for anti-atherosclerosis activity. This study evaluated the effect of rutaecarpine on endothelial dysfunction, and focused on the regulation of connexin expression in endothelial cells by rutaecarpine. Endothelia damage was induced by exposing HUVEC-12 to Ox-LDL (100mg/l) for 24h, which decreased the expression of protective proteins Cx37 and Cx40, but induced atherogenic Cx43 expression, in both mRNA and protein levels, concomitant with the impaired propidium iodide diffusion through the gap junctions. Pretreatment with rutaecarpine effectively recovered the expression of Cx37 and Cx40, but inhibited Cx43 expression, thereby improving gap junction communication and significantly prevented the endothelial dysfunction. Consequently, the cell viability and nitric oxide production were increased, lactate dehydrogenase production was decreased and monocyte adhesion was inhibited. These protective effects of rutaecarpine were remarkably attenuated by pretreatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid subtype 1 (TRPV1). In summary, this study is the first to report that rutaecarpine prevents endothelial injury and gap junction dysfunction induced by Ox-LDL in vitro, which is related to regulation of connexin expression patterns via TRPV1 activation. These results suggest that rutaecarpine has the potential for use as an anti-atherosclerosis agent with a novel mechanism.
authors: Medical college, Nanchang University, Bayi Road 461, Nanchang, Jiangxi Province 330006, PR China.
authors: Wei-Jie
authors: WJ
authors: Peng
authors: Ganzhou Cancer Hospital, Ganzhou, Jiangxi Province 341000, PR China.
authors: Yong
authors: Y
authors: Liu
authors: Medical college, Nanchang University, Bayi Road 461, Nanchang, Jiangxi Province 330006, PR China.
authors: Yan-Rong
authors: YR
authors: Yu
authors: Medical college, Nanchang University, Bayi Road 461, Nanchang, Jiangxi Province 330006, PR China.
authors: Yan-Qi
authors: YQ
authors: Fu
authors: Medical college, Nanchang University, Bayi Road 461, Nanchang, Jiangxi Province 330006, PR China.
authors: Yan
authors: Y
authors: Zhao
authors: Medical college, Nanchang University, Bayi Road 461, Nanchang, Jiangxi Province 330006, PR China.
authors: Hai-Bing
authors: HB
authors: Kuang
authors: Medical college, Nanchang University, Bayi Road 461, Nanchang, Jiangxi Province 330006, PR China.
authors: Qi-Ren
authors: QR
authors: Huang
authors: Medical college, Nanchang University, Bayi Road 461, Nanchang, Jiangxi Province 330006, PR China.
authors: Ming
authors: M
authors: He
authors: Medical college, Nanchang University, Bayi Road 461, Nanchang, Jiangxi Province 330006, PR China. Electronic address: thinker_20080502@126.com.
authors: Dan
authors: D
authors: Luo
mesh_terms: D002450:Cell Communication / Q000187:drug effects; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000009:adverse effects*; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*; D052999:Quinazolinones
chemical_list: D017630:Connexins; D026121:Indole Alkaloids; D008077:Lipoproteins, LDL; D011799:Quinazolines; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C099252:oxidized low density lipoprotein; C028632:rutecarpine; D052999:Quinazolinones
keywords: Connexin; Endothelial cells; Gap junction; Oxidized low-density lipoprotein (Ox-LDL); Rutaecarpine; Transient receptor potential vanilloid subtype 1 (TRPV1)