J Korean Med Sci.  1999 Dec;14(6):607-612. 10.3346/jkms.1999.14.6.607.

Effect of angiopeptin and aspirin on accelerated graft atherosclerosis in transplanted mouse heart

• Lee JR
• Yang JH
• Kim EK
• Seo JW

• KMID: 646035
• DOI: http://doi.org/10.3346/jkms.1999.14.6.607

Abstract

In this study of the inhibitory effects of angiopeptin and aspirin on the development of accelerated graft atherosclerosis (AGAS), 22 B10.BR mice received intra-abdominal heterotopic heart transplants from B10.A mice, without immunosuppression. Group 1 (n = 5) received no pharmacological intervention, Group 2 (n = 6) was treated with angiopeptin, Group 3 (n = 5) with aspirin, and Group 4 (n = 6) with both. There was no significant difference in the incidence of AGAS among these groups. The magnitude of intimal lesion development showed less narrowing of large vessels (> 100 microns in diameter) in groups 2 and 4--i.e. the groups received angiopeptin (Group 1 = 46.9 +/- 9.3%, Group 2 = 28.5 +/- 9.2%, Group 3 = 44.1 +/- 10.9%, Group 4 = 24.2 +/- 5.9%; p < 0.01). Comparison of the fraction of tropomyosin-positive staining cells in the intima revealed a lesser degree of staining in Group 2 (p < 0.01). No intervention was effective in preventing smooth muscle cell proliferation in the media or inflammatory cell infiltration in the adventitia. In conclusion, our data suggest that angiopeptin is effective in the direct inhibition of intimal smooth muscle cell proliferation in relatively large vessels, whereas aspirin exhibits no inhibitory role in the progression of AGAS. Angiopeptin appears to be a potential therapeutic agent for inhibiting the progression of postoperative AGAS in clinical heart transplantation.

Keyword

Heart transplantation; Atherosclerosis; Somatostatin; Aspirin; Transplantation, heterotopic; Mice, congenic

MeSH Terms

Animal
Aspirin/pharmacology*
Cardiovascular Agents/pharmacology*
Coronary Arteriosclerosis/pathology
Coronary Arteriosclerosis/immunology*
Coronary Vessels/pathology
Coronary Vessels/drug effects
Heart/drug effects*
Heart Transplantation/immunology*
Immunohistochemistry
Mice
Mice, Inbred Strains
Myocardium/pathology
Myocardium/immunology
Oligopeptides/pharmacology*
Somatostatin/pharmacology
Somatostatin/analogs & derivatives*
Transplantation, Homologous/immunology
Tropomyosin/metabolism