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: Komei Tanaka, Masahiro Ito, Makoto Kodama, Makoto Tomita, Shinpei Kimura, Makoto Hoyano, Wataru Mitsuma, Satoru Hirono, Haruo Hanawa, Yoshifusa Aizawa
• Journal: Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 16 Issue 1 Pg. 79-86 (Mar 2011) ISSN: 1940-4034 [Electronic] United States
• PMID: 21193680 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• CD4 Antigens
• Cytokines
• P-Selectin
• Polysaccharides
• Natriuretic Peptide, Brain
• fucoidan

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Autoimmune Diseases (metabolism, pathology, physiopathology, prevention & control)
• CD4 Antigens (metabolism)
• Cytokines (blood)
• Heart (drug effects, physiopathology)
• Macrophages (drug effects, immunology)
• Male
• Myocarditis (immunology, pathology, physiopathology, prevention & control)
• Myocardium (immunology, pathology)
• Natriuretic Peptide, Brain (blood)
• Organ Size (drug effects)
• P-Selectin (antagonists & inhibitors)
• Polysaccharides (pharmacology, therapeutic use)
• Random Allocation
• Rats
• Rats, Inbred Lew
• Stroke Volume (drug effects)
• T-Lymphocytes (drug effects, immunology, metabolism)