{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:51:46Z","timestamp":1791280306153,"version":"4.1.0"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"abstract":"\n BACKGROUND:<\/jats:title>\n Angiogenesis is essential for the recovery of ischemic hearts with coronary artery disease (CAD). PGPC (1-palmitoyl-2-glutamyl-sn-glycero-3-phosphocholine) is a major phospholipid oxidation product in atherosclerotic lesions. Autophagy participates in angiogenesis. However, whether PGPC affects angiogenesis in ischemic hearts by regulating autophagy remains unclear.<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n Plasma PGPC concentrations were quantified and the effects of PGPC on angiogenesis were evaluated in cultured endothelial cells and in vivo using a subcutaneous Matrigel plug assay, as well as in hindlimb ischemia and myocardial infarction models in C57BL\/6J mice. Autophagic flux and the expression and modification of proteins associated with autophagy and angiogenesis were also assessed.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Plasma PGPC levels were increased in patients with CAD, and they were positively correlated with the severity of CAD and negatively correlated with coronary collateral artery formation. PGPC inhibited endothelial cell migration and tube formation. PGPC suppressed neovascularization in Matrigel plugs and reduced blood flow recovery in hindlimb ischemia. In a mouse model of myocardial infarction, PGPC attenuated angiogenesis in the ischemic myocardium. These proangiogenic effects induced by VEGFA (vascular endothelial growth factor A) in ischemic hearts were significantly inhibited by PGPC. Mechanistically, PGPC inhibited the expression of STX17 (syntaxin 17), a crucial molecule that controls autophagosomal\u2013lysosomal fusion by promoting the acetylation and subsequent ubiquitination and degradation of STX17. PGPC upregulated the expression of NPC1 (NPC intracellular cholesterol transporter 1) through CD36 (cluster of differentiation 36). NPC1 not only promoted the acetylation and subsequent ubiquitination and degradation of STX17 through the recruitment of ACAT1 (acetyl-CoA acetyltransferase 1), but also competed with STX17 to bind VAMP8 (vesicle-associated membrane protein 8), leading to inhibition of the expression of eNOS (endothelial nitric oxide synthase), ERK1\/2 (extracellular signal-regulated kinase 1\/2), and nitric oxide production. Oxidized phospholipid-neutralizing antibody E06, STX17 overexpression, or silencing of\n NPC1<\/jats:italic>\n reversed the inhibitory effect of PGPC on angiogenesis by restoring autophagic flux.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n PGPC promotes the acetylation and subsequent ubiquitin-mediated degradation of STX17 by increasing NPC1, leading to a reduction in the level of STX17 associated with VAMP8, which inhibits autophagosomal\u2013lysosomal fusion and angiogenesis. Targeting PGPC, NPC1, or STX17 may represent novel therapeutic approaches to promote angiogenesis in patients with CAD.<\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.126.079506","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:00:16Z","timestamp":1791277216000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["The Oxidized Phospholipid PGPC Impairs Angiogenesis by Inhibiting Endothelial Autophagosomal\u2013Lysosomal Fusion Through NPC1-Induced Syntaxin 17 Acetylation and Ubiquitination"],"prefix":"10.1161","author":[{"given":"Le","family":"Li","sequence":"first","affiliation":[{"name":"Division of Cardiac Surgery (L.L., J.-J.G., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., J.-H.L., Y.L., J.-S.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9281-8692","authenticated-orcid":true,"given":"Jian-Jun","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery (L.L., J.-J.G., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., J.-H.L., Y.L., J.-S.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6870-9078","authenticated-orcid":true,"given":"Yue-Ting","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Diseases, Department of Cardiology (Y.-T.K., C.-Y.L., F.-Y.W., L.C., Z.-J.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Kai","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery (L.L., J.-J.G., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., J.-H.L., Y.L., J.-S.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-7769","authenticated-orcid":true,"given":"Yu-Peng","family":"Jian","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery (L.L., J.-J.G., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., J.-H.L., Y.L., J.-S.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery (L.L., J.-J.G., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., J.-H.L., Y.L., J.-S.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Jie","family":"Deng","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery (L.L., J.-J.G., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., J.-H.L., Y.L., J.-S.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery (L.L., J.-J.G., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., J.-H.L., Y.L., J.-S.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan-Yuan","family":"Lyu","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Diseases, Department of Cardiology (Y.-T.K., C.-Y.L., F.-Y.W., L.C., Z.-J.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., 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J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Dai","sequence":"additional","affiliation":[{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Bao","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He-Jian","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China (H.-J.X., Y.-P.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-5842","authenticated-orcid":true,"given":"Yong-Ping","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China (H.-J.X., Y.-P.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1218-7565","authenticated-orcid":true,"given":"Jia-Guo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery (L.L., J.-J.G., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., J.-H.L., Y.L., J.-S.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China (L.L., J.-J.G., Y.-T.K., W.-K.P., Y.-P.J., Y.-J.L., M.-J.D., Y.C., C.-Y.L., F.-Y.W., L.C., J.-H.L., G.D., Y.L., Z.-J.O., J.-S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9138-2966","authenticated-orcid":true,"given":"Zhi-Jun","family":"Ou","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Diseases, Department of Cardiology (Y.-T.K., C.-Y.L., F.-Y.W., L.C., Z.-J.O.), Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen 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