The Effects of Chitin/Chitosan on Human Coronary Vascular Smooth Muscle Cells and Endotherium

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10670660
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Shimane Medical University
• Principal Investigator: HONDA Masaaki Shimane Medical University, Associate Professor, 医学部, 助教授 (90127530)
• Co-Investigator(Kenkyū-buntansha): TANAKA Koichi Shimane Medical University, Instructor, 医学部, 助手 (00252924)
• Project Period (FY): 1998 – 1999
• Keywords: chitin / chitosan / coronary muscle cells / balloon catheter injury / restenosis after PTCA / angioplasty / atherosclerosis / pletelt aggregation

Research Abstract

Chitin/chitosan are known to exert promoter action of plant growth, antimicrobial action, antiseptic action, and also used as hemostatic agents, suture materials, and artificial skin, We examined the effects of chitin/chitosan on migration, proliferation of and collagen synthesis by human coronary vascular smooth muscle cells in vitro. We also examined the effects of chitin/chitosan on intimal thickness by using rabbit balloon catheter injury model in vivo.
Results 1) Chitin/chitosan solution (chitin : chitosan=20 : 80, molecular weight 1000-one million) solution inhibits migration and proliferation (measured by 3H-thymidine incorporation) of and collagen synthesis (measured by 3H-proline incorporation) by human coronary smooth muscle cells in a concentration-dependent manner. However, these inhibitory effects are not observed by chitin/chitosan solution (chitin : chitosan=50 : 50) and chitosan oligomers (n<40). 2) ADP-stimulated platelets aggregation was also inhibited in a concentration-dependent manner. 3) Attachment and proliferation of the cells cultured on the gel made from chitin/chitosan solution (chitin : chitosan=20 : 80) were also inhibited, 3) Chitin/chitosan solution (chitin : chitosan=20 : 80) resolved in ascorbic acid was given subcutaneously (25mg/kg) twice (immediately after balloon injury, and 2 weeks later) in balloon catheter injury rabbit (three times pull with 20PSI). Four weeks later, injured iliac arteries were examined histologically. The surface area of intima (intima+media) (25.0+/-7.4 vs 16.2+/-4.9, p<0.01) intima/media (43.5+/-6.4 vs 31.3+/-9.9, p<0.01) was significantly reduced by subcutaneous injection of chitin chitosan solution. 4) No obvious adverse effects were observed in blood samples. Conclusion Our data suggest possible usefulness of chitin/chitosan for prevention of restenosis after PTCT as well as after angioplasty.