Differential expression of the angiotensin-(1-12)/chymase axis in human atrial tissue.
Differential expression of the angiotensin-(1-12)/chymase axis in human atrial tissue.
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DOI：
10.1177/1753944715589717
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发表时间：
2015-08
影响因子：
2.3
通讯作者：
Ferrario CM
中科院分区：
文献类型：
--
作者：
Nagata S;Varagic J;Kon ND;Wang H;Groban L;Simington SW;Ahmad S;Dell'Italia LJ;VonCannon JL;Deal D;Ferrario CM
心脏糜酶而不是血管紧张素转换酶对人类血管紧张素(Ang)I转化为Ang II具有更高的特异性。通过证明Ang-(1-12)被糜酶裂解直接生成Ang II，揭示了一条直接生成Ang II的新途径。我们研究了44例(10名女性)心脏瓣膜病、难治性房颤或缺血性心脏病患者的心耳组织中Ang-(1-12)和糜酶基因的表达和活性。(ir-)Ang-(1-12)在左心耳的表达比右心耳高54%，这与左心耳糜酶基因转录本的丰度和糜酶的活性有关，而血管紧张素原基因的表达没有差异。超声心动图显示左房增大与心房糜酶活性高度相关，而右房增大与左房增大无关，而酪氨酸羟基酶和NPY心耳mRNAs则与心房血管紧张素原mRNAs相关。在左心病者与扩大的左房和右房相连的心耳中，较高的Ang-(1-12)表达和Chymase基因转录上调以及酶活性决定了这种替代的Ang II形成途径在伴随不良的房室重构过程中的作用。
Heart chymase rather than angiotensin converting enzyme has higher specificity for angiotensin (Ang) I conversion into Ang II in humans. A new pathway for direct cardiac Ang II generation has been revealed through the demonstration that Ang-(1-12) is cleaved by chymase to generate Ang II directly. We address here whether Ang-(1-12) and chymase gene expression and activity are detected in the atrial appendages of 44 patients (10 females) undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation or ischemic heart disease. Immunoreactive- (Ir-) Ang-(1-12) expression was 54% higher in left atrial compared to right atrial appendages and this was associated with higher abundance of left atrial appendage chymase gene transcripts and chymase activity but no differences in angiotensinogen mRNA. Atrial chymase enzymatic activity was highly correlated with left atrial but not right atrial enlargement as determined by echocardiography while both tyrosine hydroxylase and NPY atrial appendages mRNAs correlated with atrial angiotensinogen mRNAs. Higher Ang-(1-12) expression and upregulation of chymase gene transcripts and enzymatic activity from the atrial appendages connected to the enlarged left versus right atrial chambers of subjects with left heart disease defines a role of this alternate Ang II forming pathway in the processes accompanying adverse atrial and ventricular remodeling.