title: Angiopoietin-1 and C16 Peptide Attenuate Vascular and Inflammatory Responses in Experimental Allergic Encephalomyelitis.
abstract: Breakdown of normal blood-brain barrier function and accompanying vascular leakage are fundamental stages in the onset of multiple sclerosis and its animal counterpart, experimental allergic encephalomyelitis. In the present study, angiopoietin-1, an endothelial growth factor well known for its role in establishing and maintaining vascular integrity, and C16, a peptide that competitively binds to integrin αvβ3 expressed on endothelial cells, were used to treat acute experimental allergic encephalomyelitis in Lewis rats. Angiopoietin-1 was more effective than C16 for reducing inflammation-induced vascular leakage. Moreover, treatment with a combination of angiopoietin-1 and C16 resulted in greater effects, not only in alleviating inflammation and reducing axonal loss/demyelination but also in down-regulating pro-inflammatory cytokine expression and improving electrophysiological dysfunction, than treatment with either angiopoietin-1 or C16 alone. Different protective effects were observed with angiopoietin-1 and C16 treatment suggesting that these proteins target specific receptors to act through different pathways. Furthermore, angiopoietin-1 and C16 may form the basis of a promising therapeutic strategy for experimental allergic encephalomyelitis and multiple sclerosis.
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Tian
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. han00shu@zju.edu.cn.
authors.forename: Shu
authors.initials: S
authors.lastname: Han
mesh_terms: D042683:Angiopoietin-1 / Q000627:therapeutic use*; D000818:Animals; D001808:Blood Vessels / Q000473:pathology / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020214:Cerebrovascular Trauma / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D007279:Injections, Subcutaneous; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009842:Oligopeptides / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D009842:Oligopeptides; C498145:Rela protein, rat; D051996:Transcription Factor RelA