Involvement of semicarbazide-sensitive amine oxidase-mediated deamination in atherogenesis in KKAy diabetic mice fed with high cholesterol diet

P. Yu, M. Wang, Y. Deng, H. Fan, L. Shira-Bock

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Aims/hypothesis. Semicarbazide-sensitive amine oxidase has been recognised to be a potential risk factor in vascular disorders associated with diabetic complications and to be related to mortality in patients suffering from heart disease. This enzyme, associated with the vascular system, catalyses the deamination of methylamine and aminoacetone, and also acts as an adhesion molecule related to leucocyte trafficking and inflammation. The deaminated products include the toxic aldehydes, formaldehyde and methylglyoxal, respectively, hydrogen peroxide and ammonia. Materials and methods. In this study, the KKAy mouse, a strain possessing features closely resembling those of Type II (non-insulin-dependent) diabetes mellitus has been used to substantiate the hypothesis. Vascular lesions were induced via chronic feeding of a high cholesterol diet. Results. Both MDL-72974A, a selective mechanism-based semicarbazide-sensitive amine oxidase inhibitor and aminoguanidine effectively inhibited aorta semicarbazide-sensitive amine oxidase activity, and caused a substantial increase in urinary methylamine, and a decrease in formaldehyde and methylgloxal levels. Inhibition of semicarbazide-sensitive amine oxidase also reduced oxidative stress, as shown by a reduction of malondialdehyde excretion. Both MDL-72974A and aminoguanidine reduced albuminuria, proteinuria and the number of atherosclerotic lesions in animals fed with a cholesterol diet over a period of treatment for 16 weeks. Conclusion/interpretation. Increased semicarbazide-sensitive amine oxidase-mediated deamination could be involved in the cascade of atherogenesis related to diabetic complications.

Original languageEnglish
Pages (from-to)1255-1262
Number of pages8
JournalDiabetologia
Volume45
Issue number9
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Aminoguanidine
  • Atherosclerosis
  • Formaldehyde
  • Methylamine
  • Methylglyoxal
  • SSAO inhibitor
  • Semicarbazide-sensitive amine oxidase (SSAO)

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