Editorial focus: A fat contribution to RAS activation and blood pressure control: evidence from angiotensinogen conditional null mice. Focus on: "Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic
Editorial focus: A fat contribution to RAS activation and blood pressure control: evidence from angiotensinogen conditional null mice. Focus on: "Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic
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编辑焦点：脂肪对 RAS 激活和血压控制的贡献：来自血管紧张素原条件无效小鼠的证据。
DOI：
10.1152/ajpregu.00608.2011
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Rahmouni,Kamal
中科院分区：
文献类型：
--
作者：
Grobe,JustinL;Rahmouni,Kamal
肾素-血管紧张素系统(RAS)被公认为是血压的重要调节因子和心血管内环境稳定的决定因素。RAS最初是在循环中被描述的，尽管在包括肾、脑、心脏、肾上腺和血管在内的各种单个组织中都有RAS的许多或全部成分的存在[4]。这些RAS的地方版本在高血压和相关的终末器官损伤的发展和维持中的重要性已经被坚定地确立。越来越多的证据支持脂肪组织中存在局部RAS的概念(2)。血管紧张素原(AGT)基因在小鼠脂肪细胞系中的表达以及在小鼠和人类脂肪组织中的表达已被报道。脂肪酸、前列环素、糖皮质激素和交感神经系统似乎通过转录机制正向调节脂肪细胞中AGT基因的表达。脂肪组织中存在肾素和血管紧张素转换酶(ACE)的表达和活性，使局部产生血管紧张素(Ang)II成为可能。Ang II的两种亚型(AT1和AT2)受体均存在于脂肪细胞中，这一点从mRNA和蛋白质的存在以及配体结合的功能和药理学研究中都得到了证实。除了局部脂肪RAS的潜在生理意义外，脂肪来源的RAS组分，特别是AGT，对循环RAS的意义和参与也引起了人们的广泛关注。Yannikouris等人(10)的研究提供了令人信服的证据，证明脂肪来源的AGT有助于血浆AGT水平和血压调节。肝脏被认为是AGT合成的主要部位，也是循环AGT的主要来源。事实上，Stec等人(7)发现，肝脏AGT表达的消除与血浆AGT水平的显著降低(对照水平的90%)相关。然而，一些证据表明，脂肪组织可能对血浆AGT水平有显著影响。这是基于使用转基因小鼠的研究结果，转基因小鼠的AGT基因表达被限制在脂肪组织中，使用脂肪细胞特异性启动子(AP2)驱动AGT缺陷小鼠大鼠AGT基因的表达。与AGT基因敲除小鼠相比，AGT基因敲除小鼠没有检测到AGT血浆水平，并且血压较低，仅在脂肪组织中重新表达AGT的转基因小鼠有一些循环中的AGT(野生型对照的10%)，血压正常，并表现出
THE RENIN-ANGIOTENSIN SYSTEM (RAS) is well recognized as a critical regulator of blood pressure and a determinant of cardiovascular homeostasis. The RAS was originally described in the circulation, although the presence of many or all components of the RAS has been documented in a variety of individual tissues including kidney, brain, heart, adrenal gland, and blood vessels (4). The importance of these local versions of the RAS in the development and maintenance of hypertension and associated end-organ damage has been firmly established. Mounting evidence supports the concept that a local RAS is present in the adipose tissue (2). Expression of the angiotensinogen (AGT) gene has been reported in murine adipocyte cell lines as well as in murine and human adipose tissues. Fatty acids, carbaprostacyclin, glucocorticoids, and the sympathetic nervous system appear to positively regulate AGT gene expression in adipocytes by transcriptional mechanisms. The presence in adipose tissue of renin and angiotensin converting enzyme (ACE) expression and activity make possible the local production of angiotensin (ANG) II. Both subtypes of ANG II (AT1 and AT2) receptors are present in adipocytes as demonstrated by the presence of mRNA and protein and also by ligand binding functional and pharmacological studies. In addition to the potential physiological importance of the local adipose RAS, the significance and participation of adiposederived RAS components, particularly AGT, to the circulating RAS has attracted much attention. The study by Yiannikouris et al.(10) provides convincing evidence that adipose-derived AGT contributes to plasma AGT levels and blood pressure regulation.The liver is considered the primary site of AGT synthesis and the main source of circulating AGT. Indeed, Stec et al.(7) found that elimination of hepatic AGT expression was associated with a significant decrease in the plasma level of AGT (90% of control levels). However, some evidence suggests that adipose tissue may contribute significantly to plasma AGT levels. This is based on findings using transgenic mice with AGT gene expression restricted to adipose tissue using an adipocyte-specific promoter (aP2) driving the expression of a rat AGT cDNA in AGT-deficient mice (6). Compared with AGT knockout mice, which have no detectable AGT plasma levels and are hypotensive, transgenic mice re-expressing AGT only in the adipose tissue have some circulating AGT (10% of the wild-type controls), are normotensive, and exhibit re-