{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:26:27Z","timestamp":1791300387904,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,4,5]]},"abstract":"\n Background<\/jats:title>\n \n Kisspeptin\u201010 (\n KP<\/jats:styled-content>\n \u201010), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor,\n GPR<\/jats:styled-content>\n 54, have currently received much attention in relation to pre\u2010eclampsia. However, it still remains unknown whether\n KP<\/jats:styled-content>\n \u201010 could affect atherogenesis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We evaluated the effects of\n KP<\/jats:styled-content>\n \u201010 on human umbilical vein endothelial cells, human monocyte\u2010derived macrophages, human aortic smooth muscle cells in\u00a0vitro, and atherosclerotic lesions in apolipoprotein E\u2013deficient (ApoE\n \u2212\/\u2212<\/jats:sup>\n ) mice in\u00a0vivo.\n KP<\/jats:styled-content>\n \u201010 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a\n GPR<\/jats:styled-content>\n 54 antagonist.\n KP<\/jats:styled-content>\n \u201010 stimulated\n mRNA<\/jats:styled-content>\n expression of tumor necrosis factor\u2010\u03b1, interleukin\u20106, monocyte chemotactic protein\u20101, intercellular adhesion molecule\u20101, vascular adhesion molecule\u20101, and E\u2010selectin in human umbilical vein endothelial cells.\n KP<\/jats:styled-content>\n \u201010 significantly enhanced oxidized low\u2010density lipoprotein\u2013induced foam cell formation associated with upregulation of\n CD<\/jats:styled-content>\n 36 and acyl\u2010CoA:cholesterol acyltransferase\u20101 in human monocyte\u2010derived macrophages. In human aortic smooth muscle cells,\n KP<\/jats:styled-content>\n \u201010 significantly suppressed angiotensin\n II<\/jats:styled-content>\n \u2013induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (\n MMP<\/jats:styled-content>\n )\u20102 and\n MMP<\/jats:styled-content>\n \u20109 by upregulation of extracellular signal\u2010regulated kinase 1 and 2, p38, Bcl\u20102\u2010associated X protein, and caspase\u20103. Four\u2010week\u2010infusion of\n KP<\/jats:styled-content>\n \u201010 into ApoE\n \u2212\/\u2212<\/jats:sup>\n mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte\/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous\n KP<\/jats:styled-content>\n \u201010 were completely canceled by P234 infusion in ApoE\n \u2212\/\u2212<\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results suggest that\n KP<\/jats:styled-content>\n \u201010 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The\n GPR<\/jats:styled-content>\n 54 antagonist may be useful for prevention and treatment of atherosclerosis. Thus, the\n KP<\/jats:styled-content>\n \u201010\/\n GPR<\/jats:styled-content>\n 54 system may serve as a novel therapeutic target for atherosclerotic diseases.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.005790","type":"journal-article","created":{"date-parts":[[2017,4,15]],"date-time":"2017-04-15T00:20:10Z","timestamp":1492215610000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Potent Vasoconstrictor Kisspeptin\u201010 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist"],"prefix":"10.1161","volume":"6","author":[{"given":"Kengo","family":"Sato","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remina","family":"Shirai","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular 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