Angiotensin II induces a region-specific hyperplasia of the ascending aorta through regulation of inhibitor of differentiation 3.
Angiotensin II induces a region-specific hyperplasia of the ascending aorta through regulation of inhibitor of differentiation 3.
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DOI：
10.1161/circresaha.109.212837
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发表时间：
2010-02-19
影响因子：
20.1
通讯作者：
Daugherty A
中科院分区：
文献类型：
--
作者：
Owens AP 3rd;Subramanian V;Moorleghen JJ;Guo Z;McNamara CA;Cassis LA;Daugherty A
血管紧张素II （AngII）对平滑肌细胞有多种作用。影响的多样性可能与这种细胞类型的区域位置有关。本研究的目的是确定AngII是否对主动脉平滑肌细胞（SMC）产生发散性影响，并确定血压和特定氧化机制的作用。注射AngII (1000 ng/kg/min) 28天，小鼠收缩压（SBP）升高，并促进整个主动脉内侧等量扩张。这两种效应都因AT1a受体缺乏而消失。同样，给药去甲肾上腺素使血压升高，但对主动脉内侧厚度没有影响。除升主动脉增生外，大多数主动脉区域肥大导致SMC扩张，导致内侧厚度增加。缺乏NADPH氧化酶的p47phox组分可消融血管炎诱导的所有主动脉区域内侧扩张。整个主动脉的mRNA和蛋白分析显示，与其他区域相比，升主动脉中分化抑制剂3 （Id3）的丰度要高得多。Id3缺乏可抑制血管内皮素诱导的升主动脉SMC增生。总之，AngII通过氧化机制以特定区域的方式促进主动脉内侧肥大和增生。升主动脉增生依赖于Id3。
Angiotensin II (AngII) has diverse effects on smooth muscle cells. The diversity of effects may relate to the regional location of this cell type. The aim of this study was to define whether AngII exerted divergent effects on smooth muscle cells (SMC) in the aorta and determine the role of blood pressure and specific oxidant mechanisms. AngII (1,000 ng/kg/min) infusion for 28 days into mice increased systolic blood pressure (SBP) and promoted medial expansion of equivalent magnitude throughout the entire aorta. Both effects were ablated by AT1a receptor deficiency. Similar increases in blood pressure by administration of norepinephrine promoted no changes in aortic medial thickness. Increased medial thickness was due to SMC expansion attributable to hypertrophy in most aortic regions, with the exception of hyperplasia of the ascending aorta. Deficiency of the p47phox component of NADPH oxidase ablated AngII-induced medial expansion in all aortic regions. Analysis of mRNA and protein throughout the aorta revealed a much higher abundance of the inhibitor of differentiation 3 (Id3) in the ascending aorta compared to all other regions. A functional role was demonstrated by Id3 deficiency inhibiting AngII-induced SMC hyperplasia of the ascending aorta. In conclusion, AngII promotes both aortic medial hypertrophy and hyperplasia in a region-specific manner via an oxidant mechanism. The ascending aortic hyperplasia is dependent on Id3.