Macrophage-derived matrix metalloproteinase-1 enhances aortic aneurysm formation in transgenic rabbits
Manabu Niimi
Kazutoshi Nishijima
Shuji Kitajima
Fumikazu Matsuhisa
Kaneo Satoh
Hirokazu Yamazaki
Jifeng Zhang
Y.Eugene Chen
Jianglin Fan
摘要：Increased expression of matrix metalloproteinase-1 (MMP-1) has been observed in the lesions of atherosclerosis and aneurysms;however,it is not fully understood whether macrophage-derived MMP-1 affects these diseases.To investigate whether macrophage-derived MMP-1 participates in the development of vascular diseases,we generated transgenic (Tg) rabbits expressing human MMP-1 in the monocyte/macrophage lineage under the control of the human scavenger receptor enhancer/promoter.Tg rabbits exhibited no visible abnormalities throughout their bodies.Western blotting analysis revealed that the amount of MMP-1 proteins in the conditioned media secreted from peritoneal macrophages of Tg rabbits was up to 3-fold higher than that in non-Tg rabbits.For the first experiment,Tg and non-Tg rabbits were fed a cholesterol diet for 16 weeks,and aortic and coronary atherosclerosis were evaluated.The gross lesion area of aortic atherosclerosis in Tg rabbits was not significantly different from that in non-Tg rabbits,but Tg rabbits had marked destruction of the medial elastic lamina of the aortic lesions on microscopic examination.For the second experiment,we generated aortic aneurysms by incubating with elastase.Compared with non-Tg rabbits,Tg rabbits exhibited a significantly greater aortic dilation.Increased macrophage-derived MMP-1 led to increased medial destruction in both aortic atherosclerosis and aneurysms.These results demonstrate that MMP-1 plays a different role in the pathogenesis of atherosclerosis and aneurysms.
机标关键词：
分类号：R543.1(心脏、血管（循环系）疾病)
资助基金：This work was supported in part by research grants from JSPS KAKENHI(JP26460486 to MN and JP15H04718 to JF)NIH grants (R01HL117491 and R01HL129778 to YEC)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 271-279 )
英文信息