{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:58:48Z","timestamp":1781240328069,"version":"3.54.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>\n                    Ischemic heart disease (IHD) remains the leading cause of mortality worldwide, and the long-term benefits conferred by revascularization are limited. Cardiac shock wave therapy (CSWT) can promote neovascularization and attenuate myocardial injury, and has been applied in the treatment of IHD; its mechanism may involve Circulating Angiogenic cells (CACs) and their key proteins. This study aimed to explore the potential mechanism by which CSWT exerts effects on angiogenesis and attenuates structural damage following Acute Myocardial Infarction (AMI). Using\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments combined with Olink proteomics, three core regulatory proteins involved in angiogenesis, namely S100A4, CSF2, and FOXO1, were screened.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , optimized CSWT enhanced the migration and tube formation of rat bone marrow-derived CACs, as well as the expression of pro-angiogenic factors such as VEGF and HGF.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , CSWT after AMI reduced infarct size, elevated the levels of CACs (CD34\/CD133) and vascular markers (CD31\/\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -SMA), and modulated 18 differentially expressed proteins. Key regulatory factors S100A4, CSF2, and FOXO1 were identified by Olink proteomics. The expression levels of these proteins were verified by dual qPCR experiments\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The results reveal that CSWT modulates the S100A4\/CSF2\/FOXO1 network and activates CACs in AMI, suggesting a mechanistic basis for further translational evaluation of CSWT as a potential adjuvant therapy for IHD.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2026.1839337","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:40:46Z","timestamp":1781239246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracorporeal cardiac shock wave therapy modulates post-infarction neovascularization via CAC-mediated pro-angiogenic effects and modulation of the S100A4\/CSF2\/FOXO1 protein network"],"prefix":"10.3389","volume":"13","author":[{"given":"Yang","family":"Li","sequence":"first","affiliation":[{"name":"Cardiovascular Clinical Medicine Center, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Cardiovascular Clinical Medicine Center, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Second People\u2019s Hospital of Yunnan Province","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Zeng","sequence":"additional","affiliation":[{"name":"Cardiovascular Clinical Medicine Center, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Hu","sequence":"additional","affiliation":[{"name":"Cardiovascular Clinical Medicine Center, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Clinical Medicine Center, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baotong","family":"Hua","sequence":"additional","affiliation":[{"name":"Cardiovascular Clinical Medicine Center, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Cardiovascular Clinical Medicine Center, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1161\/CIRCRESAHA.113.301202","article-title":"Bone-Derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms","volume":"113","author":"Duran","year":"2013","journal-title":"Circ Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e153","DOI":"10.1161\/CIR.0000000000001052","article-title":"Heart disease and stroke statistics\u20142022 update: a report from the American Heart Association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"13492","DOI":"10.3390\/ijms252413492","article-title":"Mechanisms and therapeutic potential of multiple forms of cell death in myocardial ischemia\u2013reperfusion injury","volume":"25","author":"Tsurusaki","year":"2024","journal-title":"IJMS"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1093\/eurheartj\/ehac223","article-title":"Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies","volume":"43","author":"Frantz","year":"2022","journal-title":"Eur Heart J"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.4244\/EIJ-D-21-00192","article-title":"Temporal trends in clinical outcomes after percutaneous coronary intervention: a systematic review of 66,327 patients from 25 all-comers trials","volume":"17","author":"Asano","year":"2022","journal-title":"EuroIntervention"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.1093\/eurheartj\/ehae341","article-title":"Cardiac shockwave therapy in addition to coronary bypass surgery improves myocardial function in ischaemic heart failure: the CAST-HF trial","volume":"45","author":"Holfeld","year":"2024","journal-title":"Eur Heart J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3400\/avd.ra.20-00010","article-title":"Therapeutic angiogenesis with sound waves","volume":"13","author":"Shindo","year":"2020","journal-title":"Ann Vasc Dis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s10753-013-9712-1","article-title":"Shockwave therapy differentially stimulates endothelial cells: implications on the control of inflammation via toll-like receptor 3","volume":"37","author":"Holfeld","year":"2014","journal-title":"Inflammation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.jtcvs.2013.01.017","article-title":"Shock wave treatment induces angiogenesis and mobilizes endogenous CD31\/CD34-positive endothelial cells in a hindlimb ischemia model: implications for angiogenesis and vasculogenesis","volume":"146","author":"Tepek\u00f6yl\u00fc","year":"2013","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B11","doi-asserted-by":"publisher","first-page":"12298","DOI":"10.3390\/ijms241512298","article-title":"New insights into the reparative angiogenesis after myocardial infarction","volume":"24","author":"Mart\u00edn-B\u00f3rnez","year":"2023","journal-title":"IJMS"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2410","DOI":"10.3892\/etm.2015.2820","article-title":"Cardiac shockwave therapy improves myocardial function in patients with refractory coronary artery disease by promoting VEGF and IL-8 secretion to mediate the proliferation of endothelial progenitor cells","volume":"10","author":"Cai","year":"2015","journal-title":"Exp Ther Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"747497","DOI":"10.3389\/fcvm.2021.747497","article-title":"Extracorporeal cardiac shock waves therapy improves the function of endothelial progenitor cells after hypoxia injury via activating PI3\u2005K\/akt\/eNOS signal pathway","volume":"8","author":"Wang","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/scrt410","article-title":"Myocardial transfection of hypoxia-inducible factor-1\u03b1 and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction","volume":"5","author":"Huang","year":"2014","journal-title":"Stem Cell Res Ther"},{"key":"B15","doi-asserted-by":"publisher","first-page":"693875","DOI":"10.3389\/fcvm.2021.693875","article-title":"Cardiac shock wave therapy improves ventricular function by relieving fibrosis through PI3\u2005K\/akt signaling pathway: evidence from a rat model of post-infarction heart failure","volume":"8","author":"Wang","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/7434","article-title":"Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization","volume":"5","author":"Takahashi","year":"1999","journal-title":"Nat Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1172\/JCI23126","article-title":"Involvement of foxo transcription factors in angiogenesis and postnatal neovascularization","volume":"115","author":"Potente","year":"2005","journal-title":"J Clin Invest"},{"key":"B18","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/nm1613","article-title":"Endothelial-to-mesenchymal transition contributes to cardiac fibrosis","volume":"13","author":"Zeisberg","year":"2007","journal-title":"Nat Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1103229","DOI":"10.3389\/fvets.2023.1103229","article-title":"A review on experimental surgical models and anesthetic protocols of heart failure in rats","volume":"10","author":"Farag","year":"2023","journal-title":"Front Vet Sci"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1161\/ATVBAHA.113.301931","article-title":"Hypoxia inhibits cellular senescence to restore the therapeutic potential of old human endothelial progenitor cells via the hypoxia-inducible factor-1\u03b1\u2013TWIST-p21 axis","volume":"33","author":"Lee","year":"2013","journal-title":"ATVB"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3293","DOI":"10.1084\/jem.20170689","article-title":"The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes","volume":"214","author":"Anzai","year":"2017","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.yjmcc.2016.10.001","article-title":"S100a4 protects the myocardium against ischemic stress","volume":"100","author":"Doroudgar","year":"2016","journal-title":"J Mol Cell Cardiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1159\/000489683","article-title":"Downregulation of S100A4 alleviates cardiac fibrosis via wnt\/\u03b2 -catenin pathway in mice","volume":"46","author":"Qian","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"B24","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/s12265-010-9200-z","article-title":"Foxo, autophagy, and cardiac remodeling","volume":"3","author":"Ferdous","year":"2010","journal-title":"J of Cardiovasc Trans Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s10020-023-00662-1","article-title":"S100 proteins in cardiovascular diseases","volume":"29","author":"Zhou","year":"2023","journal-title":"Mol Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2823","DOI":"10.1161\/CIRCULATIONAHA.106.628623","article-title":"Low-Energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia","volume":"114","author":"Aicher","year":"2006","journal-title":"Circulation"},{"key":"B27","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1159\/000358652","article-title":"GM-CSF Induces cyclin D1 expression and proliferation of endothelial progenitor cells via PI3\u2005K and MAPK signaling","volume":"33","author":"Qiu","year":"2014","journal-title":"Cell Physiol Biochem"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1839337\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:40:52Z","timestamp":1781239252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1839337\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":27,"alternative-id":["10.3389\/fcvm.2026.1839337"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1839337","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]},"article-number":"1839337"}}