Evidence map›Paper›PMID 41645912›Full record

ArticleCirculation2026

Apolipoprotein D, a Novel Ligand for CD36, Is Essential for Blood-Brain Barrier Integrity.

Chang-Xiong Gong, Pei-Xia Shi, Yan-Jie Huang, Yue Dai, Lin-Lin Hu, Xiao-Feng Cheng, Shuang Zhang, Meng-Ting He, Jian-Hua Wang, Zhao-You Meng and 23 more

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Article in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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33 authors.

Chang-Xiong Gong *Department of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).
Pei-Xia Shi *Department of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0002-1069-5307
Yan-Jie Huang *Department of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0003-2007-1829
Yue Dai *ORCID 0000-0002-1349-3778
Lin-Lin HuDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0009-0000-2670-3351
Xiao-Feng ChengDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0002-7079-7612
Shuang ZhangDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).
Meng-Ting HeDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0001-8773-3167
Jian-Hua WangTsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China (M.-T.H., J.-H.W., M.-Q.D.).ORCID 0000-0002-7546-5449
Zhao-You MengDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).
Yi-Liang FangDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0003-2414-2532
Bin-Qiao WangDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0009-0001-6250-7400
Yuan ZhaoDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).
Cheng-Kang HeMedical Care Center, Shigatse Branch of Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-K.H.).
Guo-Qiang YangDepartment of Neurology, Huaihai Hospital, Xuzhou medical University, Xuzhou, China (G.-Q.Y.).
Wen-Jie ZiDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0001-6323-2659
Zhong-Ming QiuDepartment of Neurology, the 903rd Hospital of The Chinese People's Liberation Army. Hangzhou, China (Z.-M.Q.).ORCID 0000-0002-1622-9526
Feng-Li LiDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0002-0424-1499
Sen LinDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0001-9346-8187
Hui LuDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).
Chen-Hao ZhaoDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0000-0002-1625-6970
Chi ZhangDepartment of Oncology, Xinan Hospital, the Army Medical University, Chongqing, China (C.Z.).
Zhen-Yu LiuDepartment of Urology, General Hospital of central Theater Command of Chinese People's Liberation Army, Wuhan, Hubei, China (Z.-Y.L.).ORCID 0000-0002-2085-2628
Meng-Qiu DongTsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China (M.-T.H., J.-H.W., M.-Q.D.).ORCID 0000-0002-6094-1182
Qin OuyangDepartment of Medicinal Chemistry, the Army Medical University, Chongqing, China (Q.O.).ORCID 0000-0002-1161-5102
Hong-Ting ZhengDepartment of Endocrinology, Xinqiao Hospital, the Army Medical University, Chongqing, China (H.-T.Z.).ORCID 0000-0002-6930-0103
Jian-Qin NiuDepartment of Histology and Embryology, the Army Medical University, Chongqing, China (J.-Q.N., F.M.).ORCID 0000-0003-0642-7542
Feng MeiDepartment of Histology and Embryology, the Army Medical University, Chongqing, China (J.-Q.N., F.M.).ORCID 0000-0003-4125-1570
Bao-Liang SunDepartment of Neurology, the Second Affiliated Hospital, Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, China (B.-L.S.).
Jin ZhouDaping Hospital, the Army Medical University, Chongqing, China (J.Z.).
Qi XieDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).
Fang-Fei LiDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).
Qing-Wu YangDepartment of Neurology, Xinqiao Hospital, the Army Medical University, Chongqing, China (C.-X.G., P.-X.S., Y.-J.H., L.-L.H., X.-F.C., S.Z., M.-T.H., Z.-Y.M., Y.-L.F., B.-Q.W., Y.Z., W.-J.Z., F.-L.L., S.L., H.L., C.-H.Z., Q.X., F.-F.L., Q.-W.Y.).ORCID 0009-0005-4604-7335

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe disruption of the blood-brain barrier (BBB) is a central pathogenic event in many central nervous system disorders. However, the mechanisms regulating BBB function remain incompletely understood, and effective treatments are lacking. Brain mural cells differ significantly from their peripheral counterparts, a distinction likely critical for maintaining BBB integrity.

methodsWe combined proteomic profiling of human brain

resultsOur study has shown an increased expression of ApoD in mural cells after ischemic stroke. We found that mural cell-derived ApoD functions as an inhibitory ligand of endothelial CD36, suppressing pathological endothelial proliferation, preserving BBB integrity, and promoting neurological recovery. Additionally, overexpression of ApoD in mural cells improved BBB integrity and enhanced functional recovery in

conclusionsOur work identifies a previously unrecognized paracrine mechanism in which mural cell-derived ApoD directly engages endothelial CD36 to restrain pathological endothelial proliferation, thereby preserving BBB integrity and promoting neurological recovery after stroke. These findings further suggest that hypoglycosylated ApoD, with its higher CD36-binding affinity, merits investigation as a potential strategy to enhance BBB repair in central nervous system disorders.

Indexed as

Apolipoproteins DBlood-Brain BarrierCD36 AntigensIschemic StrokeAnimalsGlycosylationHumansLigandsMaleMiceMice, Inbred C57BLMice, KnockoutAPOD protein, humanApolipoproteins DCD36 AntigensCD36 protein, humanLigandsapolipoproteins Dblood-brain barrierendothelial cellsischemic stroke

Identifiers

PMID41645912
PMCPMC13056418

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.