{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:04:14Z","timestamp":1793343854727,"version":"4.5.0"},"reference-count":58,"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":[[2025,1,17]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Type A aortic dissection (TAAD) is a life-threatening condition characterized by complex pathophysiology, in which macrophages play a critical but not yet fully understood role. This study focused on the role of endothelial cells with elevated expression of ACKR1 (atypical chemokine receptor 1) and their interaction with proinflammatory macrophages in TAAD development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Single-cell transcriptomic analysis of human aortic tissues was used to identify cellular heterogeneity in TAAD. Clinical and animal studies evaluated the relationship between ACKR1 expression and TAAD severity. Gain- and loss-of-function experiments, involving modulation of ACKR1 expression in ECs, investigated its role in macrophage regulation. Molecular docking and in vitro\/in vivo studies identified and tested potential drugs targeting ACKR1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>TAAD tissues exhibited increased ECs with high ACKR1 expression and proinflammatory macrophages. High ACKR1 levels were strongly associated with TAAD severity. Knockdown of ACKR1 suppressed the NF-\u03baB (nuclear factor-\u03baB) signaling pathway and SPP1 (secreted phosphoprotein 1) expression, reducing macrophage migration and polarization, thereby inhibiting TAAD progression. Conversely, overexpression of ACKR1 exacerbated TAAD. Amikacin, identified as an ACKR1 targeted drug, regulated macrophage behavior via the ACKR1\/NF-\u03baB\/SPP1 pathway, attenuating TAAD progression and improving survival in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This study reveals how endothelial cells exhibiting high ACKR1 expression modulate macrophage migration and proinflammatory polarization through the ACKR1\/NF-\u03baB\/SPP1 signaling pathway, a crucial mechanism in TAAD progression. Targeting ACKR1 through both functional and pharmacological approaches effectively suppressed TAAD progression and extended survival in TAAD mice, offering promising new intervention strategies for clinical evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.124.325458","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T05:00:36Z","timestamp":1734498036000},"page":"211-228","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["ACKR1\n                    <sup>hi<\/sup>\n                    ECs Promote Aortic Dissection Through Adjusting Macrophage Behavior"],"prefix":"10.1161","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6385-3201","authenticated-orcid":true,"given":"Yayu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People\u2019s Hospital), Guangdong, China (Y.W., X.J., Y. 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