{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:02:26Z","timestamp":1787320946290,"version":"build-2736575974"},"reference-count":72,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Vascular inflammation triggers endothelial dysfunction, a pivotal factor in the pathogenesis of diabetic vascular complications. Complement component 1q (C1q), a crucial component of the immune system, is implicated in inflammation and immune responses. However, its role in modulating endothelial function in diabetes remains poorly understood. In this study, we aimed to investigate how C1q influences endothelial inflammation in diabetes and the underlying signaling mechanisms involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Gene expression in the aortas of streptozotocin\u2010induced mice or primary endothelial cells was detected using real\u2010time quantitative polymerase chain reaction, western blot, and immunofluorescence staining. Molecular docking identified\n                      <jats:sc>dl<\/jats:sc>\n                      \u2010citrulline as a target for C1qa. Dihydroethidium staining was used to assess vascular reactive oxygen species generation, while Evans blue staining was used to evaluate vascular permeability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Here, we demonstrated that the upregulation of C1q in the aortic endothelial cells significantly reduces the expression of Nr4a1 (orphan nuclear receptor 4a1) and activates the nuclear factor \u03baB signaling pathway, leading to vascular damage. Increasing Nr4a1 expression can mitigate C1q\u2010induced vascular injury. Additionally, the small molecule\n                      <jats:sc>dl<\/jats:sc>\n                      \u2010citrulline downregulates C1q expression and alleviates endothelial inflammation in diabetes. Overexpression of\n                      <jats:italic toggle=\"no\">Hoxa3<\/jats:italic>\n                      (homeobox a3), an upstream negative regulator of C1q transcription, protects against diabetic vascular injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Together, these findings highlight that C1q downregulation ameliorates endothelial inflammation in diabetes, providing mechanistic insights for developing therapeutic strategies against diabetic vascular complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.044979","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:12:19Z","timestamp":1776337939000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Complement 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