{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:46:16Z","timestamp":1782996376168,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270274"],"award-info":[{"award-number":["82270274"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070311"],"award-info":[{"award-number":["82070311"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371199"],"award-info":[{"award-number":["32371199"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Peripheral artery disease (PAD) is characterized by arterial narrowing that reduces limb perfusion, causing significant morbidity. The body can compensate via shear stress\u2010driven collateral artery growth (arteriogenesis). However, the primary receptors of mechanical forces on the endothelial cells in PAD remain poorly defined. Human phenome\u2011wide association study (PheWAS) shows that variants near GPR68, a gene encoding shear\u2010stress sensitive G protein\u2010coupled receptor (GPCR), are\u00a0associated with increased PAD risk. To investigate the role of GPR68 in arteriogenesis in PAD, hindlimb ischemia (HLI) was employed in inducible, endothelial cell\u2010specific\n                    <jats:italic>Gpr68<\/jats:italic>\n                    knockout mice (Gpr68 iECKO) as well as littermate controls. Impaired blood perfusion recovery, smaller collateral artery diameter, and exacerbated distal muscle injury were observed in Gpr68 iECKO. Mechanistically, these defects\n                    <jats:styled-content>we<\/jats:styled-content>\n                    re associated with a reduction in perivascular CCR2\n                    <jats:sup>+<\/jats:sup>\n                    macrophage recruitment, linked to the downregulation of\n                    <jats:italic>Spp1<\/jats:italic>\n                    ,\n                    <jats:italic>Ccl2<\/jats:italic>\n                    , and\n                    <jats:italic>Itgb3<\/jats:italic>\n                    . Pharmacological activation of Gpr68 with its agonist Compound 71 enhances monocyte adhesion to ECs via increased SPP1 in vitro. In vivo, Compound 71 accelerates perfusion recovery and mitigates ischemic tissue damage. Our findings establish that endothelial GPR68 is a critical mediator of the inflammatory\u2010remodeling program essential for arteriogenesis. We propose that pharmacological activation of GPR68 represents a novel therapeutic strategy for PAD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520244","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:09:17Z","timestamp":1773994157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial GPR68 Is Essential for Arteriogenesis and Represents a Therapeutic Target in a Model of Peripheral Artery Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Yiyan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Anesthesia The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senyi","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou 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