Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice
Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice
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DOI：
10.1161/01.atv.0000236428.91125.e6
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发表时间：
2006-09-01
影响因子：
8.7
通讯作者：
Rosenfeld, Michael E.
中科院分区：
文献类型：
--
作者：
Bennett, Brian J.;Scatena, Marta;Rosenfeld, Michael E.
目的：骨保护素（OPG）是肿瘤坏死因子（TNF）超家族的一员，在骨重建中起重要作用，在小鼠和人类动脉粥样硬化病变中均有表达。目前的研究旨在评估OPG是否在apoE（-/-）小鼠中晚期动脉粥样硬化病变的进展和钙化中起作用。方法和结果-在OPG和载脂蛋白E（OPG（-/-））均缺乏的小鼠中检查动脉粥样硬化病变面积和组成以及主动脉钙含量。apoE（-/-）小鼠）。同窝OPG（-/-）。apoE（-/-）小鼠用作对照。OPG（-/-）组无名动脉病变的平均横截面积增加。40和60周龄的apoE-/-小鼠。病变面积的增加伴随着细胞结构的减少和结缔组织（包括弹性蛋白层压层）的增加。60周龄OPG（-/-）。apoE（-/-）小鼠的病变钙化面积也增加。斑块稳定性标志物无差异。在体外，OPG诱导巨噬细胞和平滑肌细胞中的基质金属蛋白酶-9（MMP-9）的活性，并作为血清剥夺平滑肌cells.Conclusion - OPG通过防止病变大小和病变钙化的增加来抑制晚期斑块的进展。OPG可能作为一种存活因子，并可能调节血管细胞中MMP 9的产生。
Objective - Osteoprotegerin (OPG), a member of the tumor necrosis factor (TNF) superfamily of proteins, plays an important role in bone remodeling and is expressed in both mouse and human atherosclerotic lesions. The current study was designed to assess whether OPG plays a role in the progression and calcification of advanced atherosclerotic lesions in apoE(-/-) mice.Methods and Results - Atherosclerotic lesion area and composition and aortic calcium content were examined in mice deficient in both OPG and apolipoprotein E (OPG(-/-). apoE(-/-) mice) at 20, 40, and 60 weeks of age. Littermate OPG(-/-). apoE(-/-) mice were used as controls. The average cross-sectional area of lesions in the innominate arteries was increased in OPG(-/-). apoE-/- mice at 40 and 60 weeks of age. The increase in lesion area was coupled with a reduced cellularity and an increase in connective tissue including laminated layers of elastin. Sixty-week-old OPG(-/-). apoE(-/-) mice also had an increase in the area of calcification of the lesions. There were no differences in markers of plaque stability. In vitro, OPG induced matrix metalloproteinase-9 (MMP-9) activity in macrophages and smooth muscle cells and acted as a survival factor for serum-deprived smooth muscle cells.Conclusion - OPG inhibits advanced plaque progression by preventing an increase in lesion size and lesion calcification. OPG may act as a survival factor and may modulate MMP9 production in vascular cells.