{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:12:38Z","timestamp":1790741558183,"version":"4.1.0"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,7,6]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Monocytes\/macrophages orchestrate myocardial remodeling through efferocytosis, the calcium-dependent clearance of apoptotic cells. While the mechanosensitive channel Piezo1 is known to modulate calcium influx in cardiac and immune contexts, its myeloid-specific role in postinfarction healing remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Myeloid\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      -specific knockout mice (\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2206LysM<\/jats:italic>\n                      <\/jats:sup>\n                      ) were established, and left anterior descending coronary artery ligation was used to induce myocardial infarction. Cardiac function was detected by echocardiography and magnetic resonance imaging, and infarct size was measured by 2,3,5-triphenyl-tetrazolium chloride staining and hematoxylin and eosin staining. Inflammatory mediators were measured by flow cytometry, immunofluorescence, and real-time polymerase chain reaction. Intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      measurements and patch-clamp were conducted to detect calcium influx and current. Through single-cell RNA sequencing, the underlying mechanisms of efferocytosis were subsequently validated via Western blot, targeted cell transfection, and macrophage-cardiomyocyte coculture assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Myeloid-specific\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      deficiency improved cardiac function and alleviated myocardial fibrosis at 3, 14, and 28 days post-myocardial infarction. Moreover,\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      deletion increased production of antiinflammatory cytokines 3 days post-myocardial infarction. Single-cell RNA sequencing revealed that the efferocytosis-associated genes were upregulated in the\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2206LysM<\/jats:italic>\n                      <\/jats:sup>\n                      group. Mechanistically, myeloid\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      deletion enhanced Orai1 expression and calcium influx, which facilitated macrophage efferocytosis. In vitro, these changes were recapitulated by\n                      <jats:italic toggle=\"yes\">Orai1<\/jats:italic>\n                      knockdown and\n                      <jats:italic toggle=\"yes\">Orai1<\/jats:italic>\n                      overexpression in bone marrow-derived macrophages. In vivo,\n                      <jats:italic toggle=\"yes\">Orai1<\/jats:italic>\n                      knockdown impaired efferocytosis and attenuated cardiac protection, whereas\n                      <jats:italic toggle=\"yes\">Orai1<\/jats:italic>\n                      overexpression enhanced it. Furthermore,\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      deletion promoted Rac1 activation and cytoskeletal remodeling, thereby enhancing apoptotic cell clearance. In addition, myeloid\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      deletion augmented lysosomal acidification and phagosome maturation, contributing to efficient apoptotic cell degradation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our study uncovered a previously unrecognized Piezo1-Orai1-Rac1 signaling axis that regulates macrophage efferocytosis and lysosomal maturation following myocardial infarction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.328012","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:00:17Z","timestamp":1780390817000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Myeloid Piezo1 Drives Cardiac Repair Through Orai1\u2013Rac1-Dependent Efferocytosis"],"prefix":"10.1161","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6531-5511","authenticated-orcid":true,"given":"Silin","family":"Liu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."},{"name":"Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., X.P., R.W., Y.C., J.L.)."},{"name":"Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."},{"name":"Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., X.P., R.W., Y.C., J.L.)."},{"name":"Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0969-5059","authenticated-orcid":true,"given":"Bo","family":"Deng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, China (B.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintao","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."},{"name":"Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., X.P., R.W., Y.C., J.L.)."},{"name":"Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi\u2019an Jiaotong University, China (Y.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongkai","family":"Fang","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, China (C.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."},{"name":"Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., X.P., R.W., Y.C., J.L.)."},{"name":"Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianmei","family":"Pan","sequence":"additional","affiliation":[{"name":"Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., X.P., R.W., Y.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangfei","family":"Luo","sequence":"additional","affiliation":[{"name":"Innovative Research Institute of Chinese Medicine, Shandong University of Chinese Medicine, Jinan, China (S. Luo, J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rentao","family":"Wan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."},{"name":"Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., X.P., R.W., Y.C., J.L.)."},{"name":"Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2019an","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."},{"name":"Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., X.P., R.W., Y.C., J.L.)."},{"name":"Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-3041","authenticated-orcid":true,"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."},{"name":"Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China (S. Liu, H.X., J.J., Z.Z., X.P., R.W., Y.C., J.L.)."},{"name":"Innovative Research Institute of Chinese Medicine, Shandong University of Chinese Medicine, Jinan, China (S. Luo, J.L.)."},{"name":"Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China (S. Liu, H.X., J.J., Z.Z., R.W., Y.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)30925-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-111315-125315"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83822"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2017.03.013"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30959-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.55"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19272-0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni871"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0232-1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.01.024"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202304690"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-025-01475-x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.4800"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102702"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193270"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2021.01.008"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.049"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13701"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409233111"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00429-3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6324"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.125068"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817070115"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.01.050"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4198"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14146-6"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2021.102431"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21178-4"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00082-0"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1485-8"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23482-5"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.10.001"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4375127"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.05.009"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06894-8"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041694"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.018"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/35075603"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12814"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-57874-2"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep40797"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.11.007"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI123374"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311326"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.320565"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpz162"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124477"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-020-0775-5"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27874-5"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb5168"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.17177"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202510991"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.08.010"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3284"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2022.05.012"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00339.2017"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/504037"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00033.2007"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.320704"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.125.328012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:00:34Z","timestamp":1783015234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.125.328012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,7,6]]}},"alternative-id":["10.1161\/CIRCRESAHA.125.328012"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.125.328012","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]},"assertion":[{"value":"2025-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-12","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}