Matrix metalloproteinase-28 deletion amplifies inflammatory and extracellular matrix responses to cardiac aging.
Matrix metalloproteinase-28 deletion amplifies inflammatory and extracellular matrix responses to cardiac aging.
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DOI：
10.1017/s1431927611012220
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发表时间：
2012-02
影响因子：
2.8
通讯作者：
Lindsey, Merry L.
中科院分区：
文献类型：
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作者：
Ma, Yonggang;Chiao, Ying Ann;Zhang, Jianhua;Manicone, Anne M.;Jin, Yu-Fang;Lindsey, Merry L.
为了确定基质金属蛋白酶 (MMP)-28 是否介导心脏衰老，对野生型 (WT) 和 MMP-28−/− 年轻（7 ± 1 个月，n = 9 只）和老年（20 ± 2 个月，n = 7 只）雌性小鼠进行了评估。与年轻对照相比，老年 WT 小鼠左心室 (LV) 中 MMP-28 的表达增加了 42% (p < 0.05)。通过多普勒超声心动图检查，两组的左心室功能在 20 ± 2 个月时均下降。然而，多巴酚丁胺应激反应相似，表明心脏储备得以维持。血浆蛋白质组分析显示，巨噬细胞炎症蛋白 (MIP)-1α、MIP-1β 和 MMP-9 血浆水平在 WT 老年小鼠中没有变化，但在 MMP-28−/− 老年小鼠中显着升高（所有 p < 0.05），表明删除 MMP-28 后炎症状态较高。 RT2-PCR 基因阵列和免疫印迹分析表明，MMP-28−/− 老年小鼠的 LV 中 MIP-1α 和 MMP-9 基因和蛋白水平也较高（所有 p < 0.05）。与相应的年轻对照相比，WT 和 MMP-28−/− 老年小鼠的 LV 中巨噬细胞数量增加类似（均 p < 0.05）。 WT 和 MMP-28−/− 年轻小鼠和老年小鼠的胶原蛋白含量没有差异。总之，左室炎症随着年龄的增长而增加，MMP-28 缺失进一步加剧炎症和细胞外基质反应，而不改变巨噬细胞数量或胶原蛋白含量。
To determine if matrix metalloproteinase (MMP)-28 mediates cardiac aging, wild-type (WT) and MMP-28−/− young (7 ± 1 months, n = 9 each) and old (20 ± 2 months, n = 7 each) female mice were evaluated. MMP-28 expression in the left ventricle (LV) increased 42% in old WT mice compared to young controls (p < 0.05). By Doppler echocardiography, LV function declined at 20 ± 2 months of age for both groups. However, dobutamine stress responses were similar, indicating that cardiac reserve was maintained. Plasma proteomic profiling revealed that macrophage inflammatory protein (MIP)-1 α, MIP-1β and MMP-9 plasma levels did not change in WT old mice but were significantly elevated in MMP-28−/− old mice (all p < 0.05), suggestive of a higher inflammatory status when MMP-28 is deleted. RT2-PCR gene array and immunoblotting analyses demonstrated that MIP-1α and MMP-9 gene and protein levels in the LV were also higher in MMP-28−/− old mice (all p < 0.05). Macrophage numbers in the LV increased similarly in WT and MMP-28−/− old mice, compared to respective young controls (both p < 0.05). Collagen content was not different among the WT and MMP-28−/− young and old mice. In conclusion, LV inflammation increases with age, and MMP-28 deletion further elevates inflammation and extracellular matrix responses, without altering macrophage numbers or collagen content.