脂肪组织局部肾素-血管紧张素系统的调节及其在糖尿病中的作用

脂肪组织局部存在肾素-血管紧张素系统(RAS)中几乎所有的组分,这些组分不仅构成局部RAS,而且是循环中RAS各成分的重要来源.多种因素包括肥胖、胰岛素等均可以影响脂肪组织中RAS各成分的表达.脂肪组织局部RAS活性增加,可作用于脂肪细胞,抑制脂肪细胞分化及脂质代谢,并影响脂肪细胞因子分泌,同时血管紧张素可作用于周围组织,通过加重炎性反应和氧化应激等途径,导致胰岛素抵抗,参与糖尿病的病理过程.     

脂肪组织肾素-血管紧张素系统研究进展

脂肪组织可表达肾素-血管紧张素系统(RAS)的多种成分。研究表明,脂肪组织RAS可受多种因素调节,其活性成分血管紧张素Ⅱ(ANGⅡ)可促进脂肪细胞增生和肥大,使脂肪组织血流量减少,抑制脂肪分解。转基因小鼠模型实验证明脂肪组织血管紧张素原(AGT)的表达对脂肪组织含量、小鼠体重和血压均有显著影响。脂肪组织RAS在肥胖及代谢综合征中的作用以及可能的药物干预途径值得关注。     

脂肪组织肾素-血管紧张素系统研究进展

脂肪组织可表达肾素-血管紧张素系统(RAS)的多种成分。研究表明，脂肪组织RAS可受多种因素调节，其活性成分血管紧张素Ⅱ(ANGⅡ)可促进脂肪细胞增生和肥大，使脂肪组织血流量减少，抑制脂肪分解。转基因小鼠模型实验证明脂肪组织血管紧张素原(AGT)的表达对脂肪组织含量、小鼠体重和血压均有显著影响。脂肪组织RAS在肥胖及代谢综合征中的作用以及可能的药物干预途径值得关注。     

肾素-血管紧张素系统与脂肪代谢研究进展

肾素-血管紧张素系统(RAS)的多种成分可在脂肪组织中表达。在鼠类动物模型中,RAS促进脂肪细胞生长、分化,甘油三酯储存,细胞肥大,体脂沉积;而在人类成熟脂肪细胞,血管紧张素Ⅱ抑制前体脂肪细胞分化,使脂肪异位沉积在肝脏、骨骼、胰岛组织,从而形成胰岛素抵抗。抑制RAS系统的药物,如血管紧张素转换酶抑制剂、血管紧张素受体拮抗剂可能改善肥胖相关的高血压、脂代谢紊乱、胰岛素抵抗,从而减少2型糖尿病的发生。     

肺的肾素-血管紧张素系统

循环肾素一血管紧张素系统(renin-angiotensin system,RAS)是重要的血压和水电解质调节系统.近年来研究发现心脏、血管壁、肾脏和脑等组织局部也具有独立的RAS,主要调节局部组织的生长和分化.我们已经认识到局部RAS在组织损伤和修复过程中起着重要作用.在肺损伤中RAS成分的表达和血管紧张素转化酶的升高提示肺存在RAS,血管紧张素Ⅱ至少在部分上介入肺损伤反应.肺循环和肺实质中局部RAS活化可能影响肺损伤的程度.RAS基因多态性研究以及与特殊表型的关系有助于我们深入了解RAS在肺部的作用,为进一步的靶向治疗提供帮助.     

局部肾素血管紧张素系统与肺癌的研究进展

肺癌的发生发展是多因素造成的,治疗和预防也是多方面的.近年来,随着对肾素血管紧张素系统(RAS)逐步深入的研究,RAS得到了很大的更新,发现了许多新的组分,而且发现除了系统性的RAS外,肺癌局部组织微环境中也包含重要的RAS组分,并在肿瘤的发生发展及血管生成中发挥重要作用.本文就更新后的局部RAS与肺癌的发生发展机制作...     

心血管和肾上腺组织中的血管紧张素转换酶及其对血压有效控制的意义

心血管组织有肾素-血管紧张素系统(RAS)成分和局部合成这些成分的能力。血管紧张素转换酶(ACE)抑制剂的应用进一步阐明局部RAS的作用。喹那普利(quinapril)降压作用的主要机理是抑制血管ACE。     

肾素-血管紧张素系统与脂肪代谢及胰岛素抵抗的关系

近年来,内分泌研究领域的研究热点及重大进展之一,就是证实了脂肪组织的内分泌功能及其与肥胖相关疾病的关系,通过小鼠模型及人类的分子生物学研究表明,局部脂肪组织内存在相当完整的肾素-血管紧张素系统(RAS),其主要效应分子血管紧张素Ⅱ(Ang Ⅱ)可通过内分泌、旁分泌、自分泌作用参与局部体脂调节,影响脂肪代谢,形成胰岛素抵抗,表现为代谢综合征(MetS).     

局部肾素-血管紧张素系统与糖尿病肾病

RAS在糖尿病肾病(DN)发生发展中的作用是确切的,特别是肾脏局部的RAS.肾脏存在RAS的所有成分,包括:肾素(renin)、血管紧张素原(angiotensinogen、AGT)、血管紧张素Ⅰ(AngⅠ)、血管紧张素Ⅱ(AngⅡ)、ACE、血管紧张素Ⅱ1型(ATl)受体.本文将会探讨DN时此系统各个成份的变化.     

局部肾素—血管紧张素系统与糖尿病肾病

RAS在糖尿病肾病（DN）发生发展中的作用是确切的,特别是肾脏局部的RAS.肾脏存在RAS的所有成分,包括：肾素（renin）、血管紧张素原（angiotensinogen、AGT）、血管紧张素Ⅰ（AngⅠ）、血管紧张素Ⅱ（AngⅡ）、ACE、血管紧张素Ⅱ1型（ATl）受体.本将会探讨DN时此系统各个成份的变化.[第一段]     

The renin-angiotensin system: a link between obesity, inflammation and insulin resistance

The renin-angiotensin system (RAS) is classically known for its role in regulation of blood pressure, fluid and electrolyte balance. Recently, several local RASs in organs such as brain, heart, pancreas and adipose tissue have also been identified. Evidence from clinical trials suggests that in addition to anti-hypertensive effects, pharmacological inhibition of RAS also provides protection against the development of type-2 diabetes. Moreover, animal models with targeted inactivation of RAS genes exhibit improved insulin sensitivity and are protected from high-fat diet-induced obesity and insulin resistance. Because there is evidence for RAS overactivation in obesity, it is possible that RAS is a link between obesity and insulin resistance. This review summarizes the evidence and mechanistic insights on the associations between RAS, obesity and insulin resistance, with special emphasis on the role of adipose tissue RAS in the pathogenesis of metabolic derangements in obesity.     

脂肪组织局部肾素血管紧张素系统与代谢综合征

肾素-血管紧张素系统相关成分陆续在脂肪组织中发现,它们主要受能量代谢调节,与代谢综合征的发生发展有密切关系。在机体发生肥胖、高血压、高血糖和高胰岛素血症时,脂肪组织内肾素-血管紧张素系统表达增加;应用血管紧张素受体拮抗剂或血管紧张素转换酶抑制剂,通过改变脂肪细胞功能等作用,改善代谢综合征的状态。     

Local adipose tissue renin-angiotensin system

A local renin-angiotensin system (RAS) has been proposed in adipocytes. Adipocytes are a suggested source of components of the RAS, with regulation of their production related to obesity-hypertension. Both angiotensin type 1 and 2 receptors have been localized to adipocytes. Angiotensin II has been demonstrated to regulate adipocyte growth and differentiation, lipid metabolism, and expression and release of adipokines and RAS components, and to promote oxidative stress. Differences in regional expression of RAS components in visceral versus subcutaneous adipose tissue have been suggested as a link between abdominal obesity and cardiovascular disease. Finally, several studies support antihypertensive efficacy of RAS blockade in patients with type 2 diabetes and obesity. Future studies should address the role of adipocyte-specific deficiency of RAS components to definitively determine the relevance of the adipose RAS to normal physiology and to the development of hypertension.     

Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue

Recent studies have demonstrated that the rat adipose tissue expresses some of the components necessary for the production of angiotensin II (Ang II) and the receptors mediating its actions. The aim of this work is to characterize the expression of the renin-angiotensin system (RAS) components in perivascular adipose tissue and to assess differences in the expression pattern depending on the vascular bed and type of adipose tissue. We analyzed Ang I and Ang II levels as well as mRNA levels of RAS components by a quantitative RT-PCR method in periaortic (PAT) and mesenteric adipose tissue (MAT) of 3-month-old male Wistar-Kyoto rats. PAT was identified as brown adipose tissue expressing uncoupling protein-1 (UCP-1). It had smaller adipocytes than those from MAT, which was identified as white adipose tissue. All RAS components, except renin, were detected in both PAT and MAT. Levels of expression of angiotensinogen, Ang-converting enzyme (ACE), and ACE2 were similar between PAT and MAT. Renin receptor expression was five times higher, whereas expression of chymase, AT(1a), and AT(2) receptors were significantly lower in PAT compared with MAT respectively. In addition, three isoforms of the AT(1a) receptor were found in perivascular adipose tissue. The AT(1b) receptor was found at very a low expression level. Ang II levels were higher in MAT with no differences between tissues in Ang I. The results show that the RAS is differentially expressed in white and brown perivascular adipose tissues implicating a different role for the system depending on the vascular bed and the type of adipose tissue.     

Comparison of circulating and local adipose tissue renin-angiotensin system in normotensive and hypertensive obese subjects

The renin-angiotensin-aldosterone system (RAAS) plays a well-recognized role in the regulation of BP and in salt and water balance. Since hypertension affects a considerable proportion of obese patients, circulating RAAS has been studied in obese subjects with and without hypertension, albeit with conflicting results. Furthermore, attention has recently focused on the expression of the components of the Renin-angiotensin system (RAS) in some organs, including adipose tissue where it seems to be involved in the regulation of growth and differentiation. The aim of our study was to investigate circulating RAAS and adipose tissue RAS in obese patients with and without hypertension and in matched controls. PRA, and plasma and urinary aldosterone levels were measured in 35 obese, 30 hypertensive obese patients and in 20 controls. In addition, the expression of angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1) genes was studied in sc adipose tissue from 8 obese, 6 hypertensive obese and 6 healthy subjects. As previously demonstrated in other studies, there were no significant differences in the levels of circulating RAAS components in the 3 groups. As regards local RAS, interestingly, we found that AT1 gene was significantly more expressed in sc adipose tissue from obese patients with hypertension than in those without hypertension and controls. By contrast, AGT levels were similar in the 3 groups. Our data do not support the hypothesis of an involvement of circulating RAAS in the development of obesity-related hypertension. On the other hand, local RAS seems to be differently regulated in sc adipose tissue from obese patients with hypertension with respect to normotensive obese patients and controls.     

The adipose renin–angiotensin system: Role in cardiovascular disease

Several reviews have highlighted the importance of local tissue production of components of the renin–angiotensin system (RAS) [Bader, M., Ganten, D., 2008. Update on tissue renin–angiotensin systems. J. Mol. Med. 86, 615–621; Krop, M., Danser, A.H., 2008. Circulating versus tissue renin–angiotensin system: on the origin of (pro)renin. Curr. Hypertens. Rep. 10, 112–118; Paul, M., Poyan Mehr, A., Kreutz, R., 2006. Physiology of local renin–angiotensin systems. Physiol. Rev. 86, 747–803]. While the concept of tissue RAS is gaining more widespread acceptance, the concept of local angiotensin II (AngII) production, acting in coordinate or independently of the endocrine RAS, continues to be debated. The primary reasons that local AngII production has been studied by many investigators are that components of the RAS are expressed by multiple cell types, and that the endocrine RAS cannot fully explain all effects of AngII. Moreover, through the development and study of genetically altered models for over-expression or knockdown of individual RAS components within specific cell types, it is becoming increasingly more evident that local RAS contribute to effects of AngII in normal physiology and disease. The purpose of this review is to define the presence and physiological significance of a local RAS in adipose tissue in relation to cardiovascular disease.     

The role of renin-angiotensin system blockade in the management of hypertension associated with the cardiometabolic syndrome

The mounting epidemic of overweight and obesity has made understanding the relationship between excess weight and associated comorbidities more urgent. Obesity is one of the strongest predictors of the development of hypertension and is an independent risk factor for cardiovascular disease, renal disease, and diabetes mellitus. The concomitant presence of obesity and hypertension, as commonly occurs in the cardiometabolic syndrome, magnifies the risk for cardiovascular and renal disease. The term "obesity-hypertension" thus serves to underscore the link between these two deleterious conditions and to emphasize the imperative for clinical intervention. Adipose tissue is now known to produce hormones and cytokines that promote inflammation, lipid accumulation, and insulin resistance. In addition, adipose tissue contains all the components of the renin-angiotensin system (RAS), which is upregulated in the presence of obesity. Evidence implicates activation of the systemic and adipose tissue RAS, as well as the sympathetic nervous system, as key obesity-related mechanisms of hypertension and other components of the cardiometabolic syndrome. RAS blockade therefore becomes a potential therapeutic strategy in patients with obesity-related hypertension and in persons with the cardiometabolic syndrome. Clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers conducted in predominantly overweight/obese populations have demonstrated significant reductions in cardiovascular and renal disease risk among a range of at-risk patients. RAS blockade also is associated with a reduced risk of new-onset diabetes compared with other classes of antihypertensive therapy. Randomized, controlled trials conducted specifically in patients with obesity and hypertension are needed to determine the optimal therapeutic approach for these patients.     

Angiotensinogen, angiotensin II and adipose tissue development

Adipose tissue is an important source of angiotensinogen (AGT). Recent evidence shows that a local renin-angiotensinogen system (RAS) is present in human adipose tissue and may act as a distinct system from plasma RAS. In obese patients, the involvement of angiotensin II (angII) as a consequence of increased plasma AGT secreted from adipose tissue has been proposed in the development of hypertension. Another role of AGT via angII in the development of adipose tissue is supported by the following: (i) in vitro, angII stimulates the production and release of prostacyclin from adipocytes, which in turn promotes the differentiation of precursor cells into adipocytes; (ii) ex vivo and in vivo, both angII and (carba)prostacyclin promote the formation of new fat cells; and (iii) AGT -/- mice exhibit a slowing down of adipose tissue development, as compared to wild-type mice. Altogether the data are consistent with an autocrine/paracrine mechanism implicating AGT, angII and prostacyclin in adipose tissue development.     

Adipose tissue as an endocrine organ? A review of recent data related to cardiovascular complications of endocrine dysfunctions

Clinical and experimental data obtained in the last few years have modified the concept of adipose tissue as one solely directed at energy storage and release. The adipose tissue is a target organ for glucocorticoids and several studies have been carried out on the function of hypothalamic-pituitary-adrenal axis in obese subjects without conclusive results. A recent and innovative finding is that adipose tissue can produce cortisol from its inactive precursor, cortisone. The identification of leptin, a hormone synthesised by fat tissue, has ushered in the modern view of this tissue as a true endocrine organ. Leptin is produced primarily by subcutaneous and to a lesser extent by visceral adipose tissue, and has a central role in controlling body weight and, especially in regulating fat stores. Leptin is also involved in several complex functions, including physiological processes associated with puberty. Another hormone of fat tissue is angiotensinogen, which is produced in larger amounts by visceral than subcutaneous fat. Human and animals adipose tissue express a whole renin-angiotensin system (RAS). Angiotensin II, the final effector of this system is probably produced locally by adipose tissue. The function of adipose RAS is not well known. RAS can participate together with other hormones and substances, in adipocyte differentiation and fat tissue growth, but could be also involved in the pathogenesis of complications of obesity including arterial hypertension.