Increased expression of the renin-angiotensin system and mast cell density but not of angiotensin-converting enzyme II in late stages of human heart failure
Increased expression of the renin-angiotensin system and mast cell density but not of angiotensin-converting enzyme II in late stages of human heart failure
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DOI：
10.1016/j.healun.2006.04.012
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发表时间：
2006-09-01
影响因子：
8.9
通讯作者：
Jimenez, Wladimiro
中科院分区：
文献类型：
--
作者：
Batlle, Montserrat;Roig, Eulalia;Jimenez, Wladimiro
背景：肾素-血管紧张素系统（RAS）的激活与左心室功能障碍的进展有关。血管紧张素转换酶（ACE）的一种新的人类同源物，称为ACE2，已被描述，但其在人类心力衰竭（HF）中的作用尚未阐明。此外，心脏血管紧张素ii的主要形成活性是ACE还是肥大细胞释放的乳糜酶，目前还存在争议。此外，长期阻断一氧化氮（NO）合成已被证明可增加ACE活性。为了评估可能导致心室恶化过程的局部激活的血管活性介质，我们试图同时分析它们在衰竭心脏中的表达。方法：我们分析了30例接受心脏移植的心力衰竭患者和12例器官供体的左心室活检。实时聚合酶链反应法测定大鼠血清ACE、ACE2、酶切酶和内皮型一氧化氮合酶（eNOS） mRNA水平，免疫组织化学法测定肥大细胞密度。测定心房钠肽（ANP）和脑钠肽（BNP） mRNA水平作为对照。结果：衰竭心肌中ACE、chymase mRNA表达及肥大细胞密度均高于对照组，ACE2表达未见明显变化。衰竭心脏的eNOS mRNA水平较低。病理组ANP和BNP的表达均高于对照组。结论：这些数据表明血管活性系统失代偿可能导致心衰患者心肌功能的进行性损害。另一方面，ACE2 mRNA的表达在人类终末期没有改变
Background: The activation of the renin-angiotensin system (RAS) contributes to the progression of left ventricular dysfunction. A novel human homologue of the angiotensin-converting enzyme (ACE), named ACE2, has been described but its role in human heart failure (HF) has not been elucidated. Besides, there is controversy as to whether the major angiotensin II-forming-activity in heart is ACE or chymase released from mast cells. Furthermore, long-term blockade of nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess the locally activated vasoactive mediators that may contribute to the ventricular deterioration process, we sought to simultaneously analyze their expression in failing hearts.Methods: We analyzed left ventricular biopsies from 30 patients with heart failure undergoing heart transplantation and 12 organ donors. The mRNA levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were quantified by real-time polymerase chain reaction and mast cell density was assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as controls.Results: There was higher ACE and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP expression were higher in pathological than in control samples.Conclusions: These data document a decompensation of vasoactive systems that may contribute to the progressive impairment of the myocardial function in HF. On the other hand, ACE2 mRNA expression is not altered in human end-stage