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Studies have shown that ferroptosis can propagate in a wave\u2010like manner across cell populations; however, whether and how this propagation participates in the cross\u2010organ communication between lung injury and ASCVDs remains unknown. Here we developed two near\u2010infrared fluorescent probes, Cy\u2010F\u20101 and Cy\u2010F\u20102, with lung\u2010targeting and plaque\u2010targeting properties, respectively. Utilizing in vivo molecular fluorescence imaging, we explored the ferroptosis communication between lung injury and atherosclerosis (AS) by directly observing the dynamics of the ferroptosis marker, Fe\n                    <jats:sup>2+<\/jats:sup>\n                    . Imaging results found that upon exposure to CS, ferroptosis was initiated and propagated across the lung to aortic plaque regions in AS rats. In combination with biochemical and transcriptomic analyses, we have for the first time mapped a ferroptosis\u2010mediated signaling network linking both diseases: CS\u2010induced ROS accumulation \u2192 Nrf2\u2010GPX4 axis destruction \u2192 labile iron pool expansion \u2192 lung epithelial cells ferroptosis \u2192 lung inflammation injury \u2192 TNF\u2010\u03b1\/IL\u20101\u03b2\/IL\u20106 release \u2192 foam cell ferroptosis \u2192 ABCA1\/ABCG1 downregulation \u2192 exacerbated AS. This study discovers the wave\u2010guided role of ferroptosis in the crosstalk between lung injury and AS, revealing the molecular mechanism of smoking\u2010aggravated ASCVDs.\n                  <\/jats:p>","DOI":"10.1002\/anie.7388558","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T07:13:31Z","timestamp":1773990811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lighting up Ferroptosis Propagating via the Lung\u2010Heart Axis Exacerbates Cardiovascular Disease Through in Situ Imaging"],"prefix":"10.1002","volume":"65","author":[{"given":"Xiaoqing","family":"Huang","sequence":"first","affiliation":[{"name":"College of Chemistry Chemical Engineering and Materials Science Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences Shandong Normal University  Jinan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Si","sequence":"additional","affiliation":[{"name":"College of Chemistry Chemical Engineering and Materials Science Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences Shandong Normal University  Jinan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghan","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials School of Chemistry and Chemical Engineering University of Jinan  Jinan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinkao","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Chemistry Chemical Engineering and Materials Science Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences Shandong Normal University  Jinan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Shandong Provincial Clinical Research Center For Emergency and Critical Care Medicine Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Chemistry Chemical Engineering and Materials Science Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences Shandong Normal University  Jinan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-7025","authenticated-orcid":false,"given":"Bo","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Chemistry Chemical Engineering and Materials Science Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences Shandong Normal University  Jinan P. R. China"},{"name":"Laoshan Laboratory  Qingdao P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"World Health Organization. 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