title: Sulfated polysaccharide fucoidan ameliorates experimental autoimmune myocarditis in rats.
abstract: Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the initial pathologic event of experimental autoimmune myocarditis (EAM). Subsequently, various bystander inflammatory cells are recruited into the myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide fucoidan binds selectin nonselectively and blocks its function. Therefore, this study was designed to evaluate whether in vivo fucoidan treatment can improve EAM. A 21-day infusion of physiological saline or fucoidan was administrated intraperitoneally to the rats with sham operation (sham-saline, n = 5; sham-fucoidan, n = 6) or those with cardiac myosin injection (EAM-saline, n = 10; EAM-fucoidan, n = 10). After 3 weeks, fucoidan treatment improved left ventricular ejection fraction (79.04 ± 2.81 vs 65.94% ± 3.22%; P < .01 vs EAM-saline) with a reduced ratio of heart weight to body weight (4.016 ± 0.239 vs 4.975 ± 0.252 mg/g; P < .05 vs EAM-saline) in EAM. Furthermore, fucoidan treatment decreased serum levels of BNP (292.0 ± 53.4 vs 507.4 ± 89.2 ng/mL; P < .05 vs EAM-saline) and the myocarditis area (31.66 ± 1.53 vs 42.51% ± 3.24%; P < .01 vs EAM-saline) in EAM. These beneficial effects of fucoidan were accompanied by inhibition of both macrophage and CD4-positive T-cell infiltration into the myocardium. Fucoidan, a nonselective selectin blocker, attenuates the progression of EAM. This observation may be explained, at least in part, by blocking the extravasation of inflammatory cells into the myocardium.
authors.affiliation: Division of Cardiology, Department of Cardiovascular and Vital Control, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Komei
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Makoto
authors.initials: M
authors.lastname: Tomita
authors.forename: Shinpei
authors.initials: S
authors.lastname: Kimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Hoyano
authors.forename: Wataru
authors.initials: W
authors.lastname: Mitsuma
authors.forename: Satoru
authors.initials: S
authors.lastname: Hirono
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015704:CD4 Antigens / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D019007:P-Selectin / Q000037:antagonists & inhibitors; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D013318:Stroke Volume / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015704:CD4 Antigens; D016207:Cytokines; D019007:P-Selectin; D011134:Polysaccharides; D020097:Natriuretic Peptide, Brain; C007789:fucoidan