{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:57:11Z","timestamp":1790207831968,"version":"4.1.0"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2022,8,19]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>Myocardial infarction (MI) is one of the most dangerous adverse cardiovascular events. Our previous study found that lysophosphatidic acid (LPA) is increased in human peripheral blood after MI, and LPA has a protective effect on the survival and proliferation of various cell types. However, the role of LPA and its receptors in MI is less understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To study the unknown role of LPA and its receptors in heart during MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      In this study, we found that mice also had elevated LPA level in peripheral blood, as well as increased cardiac expression of its receptor LPA\n                      <jats:sub>2<\/jats:sub>\n                      in the early stages after MI. With adult and neonate MI models in global\n                      <jats:italic toggle=\"yes\">Lpar2<\/jats:italic>\n                      knockout (\n                      <jats:italic toggle=\"yes\">Lpar2<\/jats:italic>\n                      -KO) mice, we found\n                      <jats:italic toggle=\"yes\">Lpar2<\/jats:italic>\n                      deficiency increased vascular leak leading to disruption of its homeostasis, so as to impaired heart function and increased early mortality. Histological examination revealed larger scar size, increased fibrosis, and reduced vascular density in the heart of\n                      <jats:italic toggle=\"yes\">Lpar2<\/jats:italic>\n                      -KO mice. Furthermore,\n                      <jats:italic toggle=\"yes\">Lpar2<\/jats:italic>\n                      -KO also attenuated blood flow recovery after femoral artery ligation with decreased vascular density in gastrocnemius. Our study revealed that\n                      <jats:italic toggle=\"yes\">Lpar2<\/jats:italic>\n                      was mainly expressed and altered in cardiac endothelial cells during MI, and use of endothelial-specific\n                      <jats:italic toggle=\"yes\">Lpar2<\/jats:italic>\n                      knockout mice phenocopied the global knockout mice. Additionally, adenovirus-\n                      <jats:italic toggle=\"yes\">Lpar2<\/jats:italic>\n                      and pharmacologically activated LPA\n                      <jats:sub>2<\/jats:sub>\n                      significantly improved heart function, reduced scar size, increased vascular formation, and alleviated early mortality by maintaining vascular homeostasis owing to protecting vessels from leakage. Mechanistic studies demonstrated that LPA-LPA\n                      <jats:sub>2<\/jats:sub>\n                      signaling could promote endothelial cell proliferation through PI3K-Akt\/PLC-Raf1-Erk pathway and enhanced endothelial cell tube formation via PKD1-CD36 signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Our results indicate that endothelial LPA-LPA\n                      <jats:sub>2<\/jats:sub>\n                      signaling promotes angiogenesis and maintains vascular homeostasis, which is vital for restoring blood flow and repairing tissue function in ischemic injuries. Targeting LPA-LPA\n                      <jats:sub>2<\/jats:sub>\n                      signal might have clinical therapeutic potential to protect the heart from ischemic injury.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.122.321036","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T05:01:51Z","timestamp":1659502911000},"page":"388-403","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":69,"title":["LPA\n                    <sub>2<\/sub>\n                    Contributes to Vascular Endothelium Homeostasis and Cardiac Remodeling After Myocardial Infarction"],"prefix":"10.1161","volume":"131","author":[{"given":"Jianqiu","family":"Pei","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease (J.P., L.C., C.X., S.P., X.C., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."},{"name":"National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Fuwai Central-China Hospital, Central-China Branch of National Center for Cardiovascular Diseases, Zhengzhou, China (J.P., Z.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-6429","authenticated-orcid":true,"given":"Lin","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease (J.P., L.C., C.X., S.P., X.C., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."},{"name":"State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, China (L.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Center of Laboratory Medicine (F.W., X. Cong, X. Chen), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuansheng","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease (J.P., L.C., C.X., S.P., X.C., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqiang","family":"Pei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease (J.P., L.C., C.X., S.P., X.C., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery (H.G., X.S., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery (H.G., X.S., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerold","family":"Chun","sequence":"additional","affiliation":[{"name":"Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangfeng","family":"Cong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease (J.P., L.C., C.X., S.P., X.C., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."},{"name":"State Key Laboratory of Cardiovascular Disease, Center of Laboratory Medicine (F.W., X. Cong, X. Chen), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3378-5353","authenticated-orcid":true,"given":"Weiquan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Program in Molecular Medicine, Department of Internal Medicine, Division of Cardiovascular Medicine, Department of Pathology, University of Utah, Salt Lake City (W.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1189-9114","authenticated-orcid":true,"given":"Zhe","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease (J.P., L.C., C.X., S.P., X.C., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."},{"name":"Department of Cardiovascular Surgery (H.G., X.S., Z.Z.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."},{"name":"National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Fuwai Central-China Hospital, Central-China Branch of National Center for Cardiovascular Diseases, Zhengzhou, China (J.P., Z.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-1130","authenticated-orcid":true,"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Center of Laboratory Medicine (F.W., X. Cong, X. Chen), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.06.044"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024307"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040766"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318266"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93868"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003841"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10144"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-008-0760-x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa287"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20702"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2013.94"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057641"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg5159"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0594"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1191-6"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202004629"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb0202"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3778"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.023"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz305"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02021.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R046458"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365510310003265"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.16563\/j.cnki.1671-6272.2016.10.071"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.47913"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.07.006"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.038"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705025200"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2014.12.009"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.19.6921-6929.2002"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.021"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.023027"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000678"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313177"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.2741\/4148"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-326017"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1007320"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307421"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.180778"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12678"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.03.038"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P071803"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.278.3.C612"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.20.12.e127"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00902.x"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8314-9"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-09-0288"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000226"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.07.080"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0498"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10656"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.03.035"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI121955"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316711"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010818-021358"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-022-00927-z"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)05066-1"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e6409"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1412696"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09492-4"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20173"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15773"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.122.321036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T19:44:08Z","timestamp":1770061448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.122.321036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,19]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,8,19]]}},"alternative-id":["10.1161\/CIRCRESAHA.122.321036"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.122.321036","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,19]]},"assertion":[{"value":"2022-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-17","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}