Effects of losartan on atherosclerotic plaques: stability and expression of MMP-1 and its inhibitor in ApoE gene-deficient mice

AIM: To explore the effects of losartan (LST) on the expressions of matrx metalloproteinase 1 (MMP-1) and tissue inhibitor of MMP-1 (TIMP-1) in aortic atherosclerotic plaques of ApoE gene-deficient (ApoE-/-) mice and to discuss the possible mechanism of LST stabilizing atherosclerotic plaques. METHODS: Twenty seven male 8-week-old ApoE-/- mice were randomly divided into three equal groups: control group, low-dose LST ［5mg/(kg·d)］ group and high-dose LST ［25mg/(kg·d)］ group. The period of administration was 16 weeks. Serum lipid was measured by routine biochemical methods. Consecutive paraffin slices were histochemically colorated to observe the pathological changes of the atherosclerosis (As). The expressions of MMP-1 and TIMP-1 in atherosclerotic plaques were detected by immunological histochemical staining. RESULTS: No significant difference was observed in serum lipids among the three groups. Atheromatous plaques of the two treatment groups contained some thick fibrous caps and little lipid cores, characteristic of stable plaques. The expression of MMP-1 protein and the ratio of MMP-1/TIMP-1 of LST treatment groups were significantly lower than those of control group (P<0.01). Significant differences were also observed between treatment groups (P<0.01). CONCLUSION: With no effect on serum lipids, LST stabilizes plaques through decreasing the expression of MMP-1 protein and modulating the balance of MMP-1/TIMP-1. The impact of stabilizing plaques is concentration dependent.