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 be a potential risk factor of atherosclerosis. In the present study semicarbazide-sensitive amine oxidase (SSAO)-mediated MA turnover in C57BL/6 mouse, a strain very susceptible to atherosclerosis, has been assessed in comparison to a moderate, i.e. BALB/c, and resistant, i.e. CD1, mouse strains. Kidney and aorta SSAO activities were found to be significantly increased in C57BL/6 in comparison to BALB/c and CD1 mice. A significant increase of urinary MA and formaldehyde were detected in C57BL/6. [14C]MA following intravenous injection would be quickly metabolized by SSAO. The labeled formaldehyde product would cross link with proteins. C57BL/6 exhibits significantly higher labeled protein adducts than BALB/c and CD1 in response to [14C]MA. The results indicated that mice vulnerable to atherosclerosis possess an increased SSAO-mediated MA turnover. The increase of production of formaldehyde, possibly other aldehydes, may induce endothelial injury or be chronically involved in protein cross-linking and subsequent angiopathy.
Yu
P H
PH
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada. YUP@SASK.USASK.CA
Deng
Y L
YL
D000498:Allyl Compounds / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D002082:Butylamines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004036:Diet, Atherogenic; D004198:Disease Susceptibility / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005557:Formaldehyde / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008297:Male; D008744:Methylamines / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012307:Risk Factors
D000498:Allyl Compounds; D002082:Butylamines; D004791:Enzyme Inhibitors; D006146:Guanidines; D008744:Methylamines; C058000:mofegiline; D005557:Formaldehyde; C027451:methylamine; D006631:Amine Oxidase (Copper-Containing); C004479:pimagedine