Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10
Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10
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DOI：
10.1016/j.cell.2006.05.040
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发表时间：
2006-07-28
期刊：
影响因子：
64.5
通讯作者：
Olson, Eric N.
中科院分区：
文献类型：
--
作者：
Chang, Shurong;Young, Bryan D.;Olson, Eric N.
心血管系统的发育和稳态需要内皮细胞和平滑肌细胞之间的密切相互作用，形成无缝的循环网络。我们发现，组蛋白脱乙酰酶7（HDAC 7）是专门表达在血管内皮细胞在早期胚胎发生，在那里它保持血管的完整性，通过抑制基质金属蛋白酶（MMP）10，分泌的内切蛋白酶，降解细胞外基质的表达。小鼠HDAC 7基因的破坏导致胚胎死亡，这是由于内皮细胞-细胞粘附失败以及随后的血管扩张和破裂。HDAC 7通过与肌细胞增强因子-2（MEF 2）结合来抑制MMP 10基因转录，MEF 2是MMP 10转录的直接激活剂和血管发育的重要调节剂。这些发现揭示了HDAC 7在维持血管完整性方面的意想不到的特定作用，并对了解心血管发育和疾病期间的血管生成和血管重塑过程具有重要意义。
Development and homeostasis of the cardiovascular system require intimate interactions between endothelial and smooth muscle cells, which form a seamless circulatory network. We show that histone deacetylase 7 (HDAC7) is specifically expressed in the vascular endothelium during early embryogenesis, where it maintains vascular integrity by repressing the expression of matrix metalloproteinase (MMP) 10, a secreted endoproteinase that degrades the extracellular matrix. Disruption of the HDAC7 gene in mice results in embryonic lethality due to a failure in endothelial cell-cell adhesion and consequent dilatation and rupture of blood vessels. HDAC7 represses MMP10 gene transcription by associating with myocyte enhancer factor-2 (MEF2), a direct activator of MMP10 transcription and essential regulator of blood vessel development. These findings reveal an unexpected and specific role for HDAC7 in the maintenance of vascular integrity and have important implications for understanding the processes of angiogenesis and vascular remodeling during cardiovascular development and disease.