{"id":7867,"date":"2024-10-15T15:00:25","date_gmt":"2024-10-15T20:00:25","guid":{"rendered":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/?p=7867"},"modified":"2024-10-15T15:00:28","modified_gmt":"2024-10-15T20:00:28","slug":"ccl2-mediated-endothelial-injury-drives-cardiac-dysfunction-in-long-covid","status":"publish","type":"post","link":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/2024\/10\/15\/ccl2-mediated-endothelial-injury-drives-cardiac-dysfunction-in-long-covid\/","title":{"rendered":"CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID"},"content":{"rendered":"<div class=\"panel body-content\"><div class=\"panel__container\">\n<p><a href=\"https:\/\/www.nature.com\/articles\/s44161-024-00543-8\">Nature<\/a> Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably\u00a0<em>CCL2<\/em>. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by\u00a0<em>CCL2<\/em>. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked\u00a0<em>CCL2<\/em>\u00a0to \u2018phenotype switching\u2019 and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.<br><br><\/p>\n<\/div><\/div>","protected":false},"excerpt":{"rendered":"<p>Nature Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled [&hellip;]<\/p>\n","protected":false},"author":11,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[16],"tags":[],"class_list":["post-7867","post","type-post","status-publish","format-standard","hentry","category-published-research"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/posts\/7867","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/users\/11"}],"replies":[{"embeddable":true,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/comments?post=7867"}],"version-history":[{"count":1,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/posts\/7867\/revisions"}],"predecessor-version":[{"id":7868,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/posts\/7867\/revisions\/7868"}],"wp:attachment":[{"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/media?parent=7867"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/categories?post=7867"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/tags?post=7867"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}