The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a...The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.展开更多
Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of ...Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.展开更多
AIM： To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system （RAS） components and hemodynamic changes. METHODS： P...AIM： To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system （RAS） components and hemodynamic changes. METHODS： Patients were allocated into 4 groups： mild-to-moderate liver disease （MLD）, advanced liver disease （ALD）, patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity （PRA）, angiotensin （Ang） Ⅰ, Ang Ⅱ, and Ang-（1-7） levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components. RESULTS： PRA and angiotensins were elevated in ALD when compared to MLD and controls （P 〈 0.05）. In contrast, Ang Ⅱ was significantly reduced in MLD. Ang-（1-7）/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-（1-7）/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation （0.52 ± 0.08 vs 0.38 ±0.04, P 〈 0.02）, whereas the peripheral circulating Ang Ⅱ/Ang Ⅰ ratio was elevated in comparison to splanchnic levels （0.18 ±0.02 vs 0.13 ±0.02, P 〈 0.04）. Ang-（1-7）/ Ang Ⅱ ratios positively correlated with cardiac output （r = 0.66） and negatively correlated with systemic vascular resistance （r = -0.70）. CONCLUSION： Our findings suggest that the relationship between Ang-（1-7） and Ang Ⅱ may play a role in the hemodynamic changes of human cirrhosis.展开更多
The renin-angiotensin system(RAS) regulates blood pressure(BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at l...The renin-angiotensin system(RAS) regulates blood pressure(BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at least six receptors. Out of these, angiotensin Ⅱ, angiotensin converting enzyme 1 and angiotensin Ⅱ type 1 receptor(AngⅡ-ACE1-AT1R) together with angiotensin(1-7), angiotensin converting enzyme 2 and Mas receptor(Ang(1-7)-ACE2-Mas R) are regarded as the main components of RAS. In addition to circulating RAS, local RA-system exists in various organs. Local RA-systems are regarded as tissue-specific regulatory system accounting for local effects and long term changes in different organs. Many of the central components such as the two main axes of RAS: AngⅡ-ACE1-AT1 R and Ang(1-7)-ACE2-Mas R, have been identified in the human eye. Furthermore, it has been shown that systemic antihypertensive RAS- inhibiting medications lower intraocular pressure(IOP). These findings suggest the crucial role of RAS not only in the regulation of BP but also in the regulation of IOP, and RAS potentially plays a role in the development of glaucoma and antiglaucomatous drugs.展开更多
基金Supported by CNPq,No.460334/2014-0FAPEMIG,No.CDS-PPM-00555-15(to Simoes e Silva AC)2016 NARSAD Young Investigator Grant Awardee from the Brain and Behavior Research Foundation,No.25414(to Miranda AS)
文摘The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.
文摘Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.
基金Supported by Fundacode Amparo à Pesquisa do Estado de Minas Gerais, Conselho Nacional de Desenvolvimento Científico e Tecnológico, FAPEMIG/CNPQ-PRONEX (Grupos de Excelência),Ministério de Ciência e Tecnologia/CNPq/ FAPEMIG-INCT-Nano-Biofar
文摘AIM： To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system （RAS） components and hemodynamic changes. METHODS： Patients were allocated into 4 groups： mild-to-moderate liver disease （MLD）, advanced liver disease （ALD）, patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity （PRA）, angiotensin （Ang） Ⅰ, Ang Ⅱ, and Ang-（1-7） levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components. RESULTS： PRA and angiotensins were elevated in ALD when compared to MLD and controls （P 〈 0.05）. In contrast, Ang Ⅱ was significantly reduced in MLD. Ang-（1-7）/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-（1-7）/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation （0.52 ± 0.08 vs 0.38 ±0.04, P 〈 0.02）, whereas the peripheral circulating Ang Ⅱ/Ang Ⅰ ratio was elevated in comparison to splanchnic levels （0.18 ±0.02 vs 0.13 ±0.02, P 〈 0.04）. Ang-（1-7）/ Ang Ⅱ ratios positively correlated with cardiac output （r = 0.66） and negatively correlated with systemic vascular resistance （r = -0.70）. CONCLUSION： Our findings suggest that the relationship between Ang-（1-7） and Ang Ⅱ may play a role in the hemodynamic changes of human cirrhosis.
基金Supported by Päivikki and Sakari Sohlberg Foundationthe Eye Foundation+2 种基金the Glaucoma Research Foundation Luxthe Competitive Research Funding of Tampere University Hospital,No.9S072and the Foundation for Clinical Chemistry Research.
文摘The renin-angiotensin system(RAS) regulates blood pressure(BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at least six receptors. Out of these, angiotensin Ⅱ, angiotensin converting enzyme 1 and angiotensin Ⅱ type 1 receptor(AngⅡ-ACE1-AT1R) together with angiotensin(1-7), angiotensin converting enzyme 2 and Mas receptor(Ang(1-7)-ACE2-Mas R) are regarded as the main components of RAS. In addition to circulating RAS, local RA-system exists in various organs. Local RA-systems are regarded as tissue-specific regulatory system accounting for local effects and long term changes in different organs. Many of the central components such as the two main axes of RAS: AngⅡ-ACE1-AT1 R and Ang(1-7)-ACE2-Mas R, have been identified in the human eye. Furthermore, it has been shown that systemic antihypertensive RAS- inhibiting medications lower intraocular pressure(IOP). These findings suggest the crucial role of RAS not only in the regulation of BP but also in the regulation of IOP, and RAS potentially plays a role in the development of glaucoma and antiglaucomatous drugs.
