{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:11:53Z","timestamp":1789873913709,"version":"4.0.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2008,2,29]]},"abstract":"<jats:p>\n            Extensive research on the role of ADP in platelet activation led to the design of new anti-thrombotic drugs, such as clopidogrel (Plavix; sanofi-aventis); however, very little is known about the ADP-preferring nucleotide receptors (P2Y\n            <jats:sub>1<\/jats:sub>\n            , P2Y\n            <jats:sub>12<\/jats:sub>\n            , and P2Y\n            <jats:sub>13<\/jats:sub>\n            ) in endothelium. Here, we show that ADP stimulates migration of cultured human umbilical vein endothelial cells (HUVECs) in both Boyden chamber and in vitro wound repair assays. This promigratory effect was mimicked by 2-MeSADP, but not by AMP, and was inhibited by MRS2179 (P2Y\n            <jats:sub>1<\/jats:sub>\n            receptor antagonist) but not by AR-C69931MX (P2Y\n            <jats:sub>12\/13<\/jats:sub>\n            receptor antagonist). RT-PCR revealed abundant P2Y\n            <jats:sub>1<\/jats:sub>\n            , barely detectable P2Y\n            <jats:sub>12<\/jats:sub>\n            , and absent P2Y\n            <jats:sub>13<\/jats:sub>\n            receptor message in these cells. In addition, both ADP and 2-MeSADP, but not AMP, activated the mitogen-activated protein kinase pathways as evidenced by increased phosphorylation of extracellular signal-regulated kinase (ERK)1\/2, c-Jun N-terminal kinase (JNK), and p38 kinase. ADP also stimulated phosphorylation of p90RSK, a downstream substrate of phosphorylated ERK1\/2, and induced phosphorylation of such transcription factors downstream of the JNK and p38 pathways as c-Jun and activating transcription factor-2. These signaling events were inhibited by MRS2179 but not by AR-C69931MX. Furthermore, blockade of the ERK or JNK pathways by U0126 and SP600125, respectively, abolished ADP- and 2-MeSADP\u2013stimulated HUVEC migration. However, inhibition of the p38 pathway by SB203580 partially suppressed ADP- and 2-MeSADP\u2013induced HUVEC migration. We conclude that ADP promotes human endothelial cell migration by activating P2Y\n            <jats:sub>1<\/jats:sub>\n            receptor\u2013mediated MAPK pathways, possibly contributing to reendothelialization and angiogenesis after vascular injury.\n          <\/jats:p>","DOI":"10.1161\/circresaha.107.165795","type":"journal-article","created":{"date-parts":[[2008,1,4]],"date-time":"2008-01-04T01:55:20Z","timestamp":1199411720000},"page":"448-456","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["ADP Stimulates Human Endothelial Cell Migration via P2Y\n            <sub>1<\/sub>\n            Nucleotide Receptor\u2013Mediated Mitogen-Activated Protein Kinase Pathways"],"prefix":"10.1161","volume":"102","author":[{"given":"Jianzhong","family":"Shen","sequence":"first","affiliation":[{"name":"From the Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"DiCorleto","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic Foundation, 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