Endogenous formaldehyde as a potential factor of vulnerability of atherosclerosis: involvement of semicarbazide-sensitive amine oxidase-mediated methylamine turnover

The mouse is known to be highly resistant to atherosclerosis. However, some inbred mouse strains are vulnerable to atherosclerosis when they are fed a high-cholesterol, high-fat diet. Increased deamination of methylamine (MA) and the subsequent production of formaldehyde has been recently shown to b e a potential risk factor of atherosclerosis. In the present study semicarb azide-sensitive amine oxidase (SSAO)-mediated MA turnover in C57BL/6 mouse, a strain very susceptible to atherosclerosis, has been assessed in compari son to a moderate, i.e. BALB/c, and resistant, i.e. CD1, mouse strains. Kid ney and aorta SSAO activities were found to be significantly increased in C 57BL/6 in comparison to BALB/c and CD1 mice. A significant increase of urin ary MA and formaldehyde were detected in C57BL/6. [C-14]MA following intrav enous injection would be quickly metabolized by SSAO. The labeled formaldeh yde product would cross link with proteins. C57BL/6 exhibits significantly higher labeled protein adducts than BALB/c and CD1 in response to [C-14]MA. The results indicated that mice vulnerable to atherosclerosis possess an i ncreased SSAO-mediated MA turnover. The increase of production of formaldeh yde, possibly other aldehydes, may induce endothelial injury or be chronica lly involved in protein cross-linking and subsequent angiopathy. (C) 1998 E lsevier Science Ireland Ltd. All rights reserved.