The semicarbazide-sensitive amine oxidase (SSAO): A new actor in atherosclerosis in the APOE mouse model?

Abstract

The expression of « semicarbazide sensitive amine oxidase » (SSAO), an enzyme which transforms primary amines into aldehydes, ammonia and hydrogen peroxide, increases during smooth muscle cell differentiation (VSMC) and is widely expressed in the media layer from the arterial wall. The SSAO has been implicated in LDL oxidation and in inflammation. We hypothesized that the absence of SSAO should prevent the development of atherosclerosis. The progression of the disease and the implicated mechanisms were studied in double ApoE/SSAO knock out mice (ApoE-/-SSAO-/-) established in the laboratory. Surprisingly 25 week-old ApoE-/-SSAO-/mice presented a significant 50 % increase in plaque surface associated with an 80% decrease in a-actin expression in the media of aortic sinus from ApoE-/-SSAO-/mice compared to ApoE-/mice. We noticed a small T-cell infiltration in the media from ApoE-/-SSAO-/mice whereas no T-cell infiltration was observed in the media from ApoE-/mice. No difference was detected in monocytes/ macrophages infiltration in the plaque in aortic sinus from APOE-/-SSAO-/mice and ApoE-/-. The pro(TNFa and INFg) and anti-inflammatory (IL10 and TGFb) cytokine expressions were similar in the spleen from ApoE-/and ApoE-/-SSAO-/measured at 25 and 15 week old. In conclusion, the absence of the SSAO increases the atherosclerosis in ApoE-/mice. This result could be explained either by a modification of VSMC phenotype or to an increase in VSMC apoptosis in inflammatory situation. Thus, the SSAO could be a new potential actor implicated in the inhibition of atherosclerosis development.