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Hepatic angiotensin

Brenda de Oliveira da Silva, Luciane Carla Alberici, Letícia Ferreira Ramos, Caio Mateus Silva, Marina Bonfogo da Silveira, Carlos R P Dechant, Scott L Friedman, Kumiko Koibuchi Sakane, Letícia Rocha Gonçalves, Karen C M Moraes
The development of new therapeutic strategies to control or reverse hepatic fibrosis requires thorough knowledge about its molecular and cellular basis. It is known that the heptapeptide angiotensin-(1-7) [ang-(1-7)] can reduce hepatic fibrosis and steatosis in vivo; therefore, it is important to uncover the mechanisms regulating its activity and cellular model of investigation. Ang-(1-7) is a peptide of the renin-angiotensin system (RAS), and here we investigated its modulatory effect on the expression pattern of microRNAs (miRNAs) in hepatic stellate cells (HSCs) LX-2, which transdifferentiate into fibrogenic and proliferative cells...
March 7, 2018: International Journal of Biochemistry & Cell Biology
Shinji Takai, Denan Jin
Non-alcoholic steatohepatitis (NASH) is characterized by inflammation and fibrosis, in addition to steatosis, of the liver, but no therapeutic agents have yet been established. The mast cell protease chymase can generate angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β, all of which are associated with liver inflammation or fibrosis. In animal models of NASH, augmented chymase has been observed in the liver. In histological analysis, chymase inhibitor prevented hepatic steatosis, inflammation, and fibrosis...
2018: Frontiers in Pharmacology
Celeste Trejo Moreno, Gabriela Castro Martínez, Marisol Méndez Martínez, Jesús Enrique Jiménez Ferrer, José Pedraza Chaverri, Gerardo Arrellín, Alejandro Zamilpa, Omar Noel Medina Campos, Galia Lombardo Earl, Gerardo Joel Barrita Cruz, Beatriz Hernández, Christian Carlos Ramírez, María Angélica Santana, Gladis Fragoso, Gabriela Rosas
ETHNOPHARMACOLOGICAL RELEVANCE: A recent ethnomedical survey on medicinal plants grown in Mexico revealed that Sechium edule (Jacq.) Sw. (Cucurbitaceae) is one of the most valued plant species to treat cardiovascular diseases, including hypertension. Fruits, young leaves, buds, stems, and tuberous roots of the plant are edible. Considering that endothelial dysfunction induced by Angiotensin II plays an important role in the pathogenesis of hypertension and is accompanied by a prooxidative condition, which in turn induces an inflammatory state, vascular remodeling, and tissue damage, and that S...
March 1, 2018: Journal of Ethnopharmacology
Sergei M Danilov, Victoria E Tikhomirova, Roman Metzger, Irina A Naperova, Tatiana M Bukina, Ozlem Goker-Alpan, Nahid Tayebi, Nurshat M Gayfullin, David E Schwartz, Larisa M Samokhodskaya, Olga A Kost, Ellen Sidransky
BACKGROUND: Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. METHODS: ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes...
February 17, 2018: Molecular Genetics and Metabolism
Huijing Yao, Chunqing Zhang
BACKGROUND: Randomized controlled trials (RCTs) showed inconsistent results regarding the efficacy of angiotensin II receptor blockers (ARBs) on portal pressure as indicated by hepatic venous pressure gradient (HVPG). METHODS: A meta-analysis of RCTs was performed to evaluate the influence of ARBs treatment on HVPG. PubMed, Embase, and Cochrane's Library were searched for relevant RCTs. A fixed or a randomized effect model was used to pool the results according the heterogeneity...
February 22, 2018: Irish Journal of Medical Science
Kwang Yong Shim, Young Woo Eom, Moon Young Kim, Seong Hee Kang, Soon Koo Baik
The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang-(1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension...
February 21, 2018: Korean Journal of Internal Medicine
Ochuko L Erukainure, Rahman M Hafizur, Nurul Kabir, M Iqbal Choudhary, Olubunmi Atolani, Priyanka Banerjee, Robert Preissner, Chika I Chukwuma, Aliyu Muhammad, Eric O Amonsou, Md Shahidul Islam
Type 2 diabetes is the most prominent of all diabetes types, contributing to global morbidity and mortality. Availability and cost of treatment with little or no side effect especially in developing countries, remains a huge burden. This has led to the search of affordable alternative therapies especially from medicinal plants. In this study, the antidiabetic effect of the methanolic extract, dichloromethane (DCM), butanol (BuOH) and aqueous fractions of Clerodendrum volubile leaves were investigated in type 2 diabetic rats for their effect on glucose homeostasis, serum insulin level and hepatic biomarkers, lipid profile, pancreatic redox balance and Ca 2+ levels, and β-cell distribution and function...
2018: Frontiers in Pharmacology
Pierre Grumet, Laurent Kodjikian, Audrey de Parisot, Marie-Hélène Errera, Neila Sedira, Emmanuel Heron, Laurent Pérard, Pierre-Loïc Cornut, Christelle Schneider, Sophie Rivière, Priscille Ollé, Grégory Pugnet, Pascal Cathébras, Pierre Manoli, Bahram Bodaghi, David Saadoun, Stéphanie Baillif, Nathalie Tieulie, Marc Andre, Frédéric Chiambaretta, Nicolas Bonin, Philip Bielefeld, Alain Bron, Frédéric Mouriaux, Boris Bienvenu, Stéphanie Vicente, Sylvie Bin, Marc Labetoulle, Christiane Broussolle, Yvan Jamilloux, Evelyne Decullier, Pascal Sève
PURPOSE: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. METHODS: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis...
February 7, 2018: Autoimmunity Reviews
Sameh Saber, Amr A A Mahmoud, Noha Said Helal, Eman El-Ahwany, Rasha Abdelghany
Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl4-induced liver fibrosis. Mice were treated with silymarin (30 mg kg-1), perindopril (1 mg kg-1), fosinopril (2 mg kg-1), or losartan (10 mg kg-1). The administration RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline...
February 9, 2018: Canadian Journal of Physiology and Pharmacology
Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Yasushi Okura, Naotaka Shimozato, Shinya Sato, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Yasuhiko Sawada, Takemi Akahane, Soichiro Saikawa, Keisuke Nakanishi, Takuya Kubo, Masanori Furukawa, Ryuichi Noguchi, Kiyoshi Asada, Koh Kitagawa, Takahiro Ozutsumi, Yuki Tsuji, Daisuke Kaya, Yukihisa Fujinaga, Hitoshi Yoshiji
The farnesoid X receptor (FXR) agonist, a bile acid-activated nuclear receptor, has been shown to improve the histologic features of nonalcoholic steatohepatitis (NASH); however, a satisfactory effect on hepatic fibrosis has not been achieved. We aimed to investigate the combined effect of FXR agonist and angiotensin II type 1 receptor blocker on hepatic fibrogenesis in rat models of NASH. For 8 weeks, two rat models of NASH were developed. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were administered intraperitoneal injections of 1 mL/kg pig serum (PS) twice a week, whereas Fischer-344 rats were fed a choline-deficient, L-amino acid-defined diet (CDAA)...
November 2017: Hepatology Communications
Hongli Xiao, Xiaoya Liu, Yan Wang, Guoxing Wang, Chenghong Yin
The pathological mechanism of lipopolysaccharide (LPS)‑induced liver injury involves a number of inflammatory mediators and cytokines. Angiotensin (Ang)‑(1‑7), a ligand for the proto‑oncogene Mas (Mas) receptor, antagonizes the actions of Ang II in the renin angiotensin system and exerts an anti‑inflammatory effect on LPS‑induced macrophages. The present study investigated the potential role of Ang‑(1‑7) in the regulation of inflammatory responses in LPS‑induced hepatocytes using the rat liver BRL cell line...
January 31, 2018: Molecular Medicine Reports
Qing-Lan Ling, Anita J Mohite, Emma Murdoch, Hironari Akasaka, Qun-Ying Li, Shui-Ping So, Ke-He Ruan
Vascular prostanoids, isomerized from an intermediate prostaglandin (PG), H2, produced by cyclooxygenase (COX), exert various effects on the vascular system, both protective and destructive. During endothelial dysfunction, vascular protector prostacyclin/prostaglandin I2 (PGI2) is decreased, while inflammatory PGE2 and thrombotic TXA2 are increased. Therefore, our research aim was to reverse the event by controlling PGH2 metabolism by generating an in vivo model via enzymatic engineering of COX-1 and prostacyclin synthase (PGIS)...
January 26, 2018: Scientific Reports
Aline Silva Miranda, Ana Cristina Simões E Silva
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...
December 28, 2017: World Journal of Gastroenterology: WJG
Dariush Mozaffarian, Jason H Y Wu
A growing body of nutritional science highlights the complex mechanisms and pleiotropic pathways of cardiometabolic effects of different foods. Among these, some of the most exciting advances are occurring in the area of flavonoids, bioactive phytochemicals found in plant foods; and in the area of dairy, including milk, yogurt, and cheese. Many of the relevant ingredients and mechanistic pathways are now being clarified, shedding new light on both the ingredients and the pathways for how diet influences health and well-being...
January 19, 2018: Circulation Research
Shuang-Yu Lv, Binbin Cui, Wei-Dong Chen, Yan-Dong Wang
Apelin, a new bioactive peptide, was identified as an endogenous ligand for APJ (Angiotensin II receptor-like 1). Apelin and its receptor have an abundant distribution in central nervous system and peripheral tissues, including liver. Apelin/APJ has diverse physiological and pathological effects, including regulation of cardiovascular function, angiogenesis, fluid homeostasis and so on. Apelin/APJ system may act as a novel potential therapeutic target for liver disease. In this article, we review the role of apelin/APJ system in liver fibrosis, hepatitis, hepatic cirrhosis, liver injury and metabolic liver disease...
December 19, 2017: Oncotarget
Xiao-Ya Li, Yan Peng, Xia-Wei Bu, Jia Yao, Li Yao
OBJECTIVE: To explore the effect of Biejiajian Oral Liquid (, BOL) on CCl4-induced hepatic fibrosis in rats by detecting the changes in the levels of angiotensin II (Ang II), angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE), ACE2, angiotensin II type 1 receptor (AT1R), Mas, etc. METHODS: A total of 180 Wistar rats were randomly divided into two groups by random digital table method: prevention experiment and treatment experiment. Each group was further subdivided into the following 6 subgroups: normal control group, model group, vitamin E [100 mg/(kg•d), VE] group, enalapril [10 mg/(kg•g), Ena] group, high-dosage [20 g/(kg•d)] BOL group, and low-dosage [10 g/(kg•d)] BOL group...
January 15, 2018: Chinese Journal of Integrative Medicine
Yuta Miyaoka, Denan Jin, Keitaro Tashiro, Shinsuke Masubuchi, Maiko Ozeki, Fumitoshi Hirokawa, Michihiro Hayashi, Shinji Takai, Kazuhisa Uchiyama
Nonalcoholic steatohepatitis (NASH), in which there is steatosis and fibrosis in the liver, is linked to metabolic syndrome and progresses to hepatic cirrhosis. In this study, a novel hamster NASH model derived from metabolic syndrome was made using hamsters. Hamsters were fed a normal or a high-fat and high-cholesterol (HFC) diet for 12 weeks. Body weight and the ratio of liver weight to body weight were significantly greater in HFC diet-fed hamsters than in normal diet-fed hamsters. Triglyceride, low-density lipoprotein cholesterol, and glucose levels in blood were significantly increased in HFC diet-fed hamsters, and blood pressure also tended to be high, suggesting that the HFC diet-fed hamsters developed metabolic syndrome...
January 1, 2018: Experimental Animals
Liwei Ren, Yuan Sun, Hong Lu, Dien Ye, Lijuan Han, Na Wang, Alan Daugherty, Furong Li, Miaomiao Wang, Fengting Su, Wenjun Tao, Jie Sun, Noam Zelcer, Adam E Mullick, Ah J Danser, Yizhou Jiang, Yongcheng He, Xiongzhong Ruan, Xifeng Lu
Rationale: An elevated level of plasma low-density lipoprotein (LDL) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDL receptor (LDLR) and SORT1, independently of the renin-angiotensin system. Objective: To investigate the physiological role of [P]RR in lipid metabolism in vivo. Methods and Results: We used N-Acetylgalactosamine (GalNAc) modified antisense oligonucleotides (ASO) to specifically inhibit hepatic [P]RR expression in C57BL/6J mice, and studied the consequences this has on lipid metabolism...
January 4, 2018: Circulation Research
Samra Joke Sanni, Christina Lyngsø, Steen Gammeltoft, Jakob Lerche Hansen
The angiotensin II type I receptor (AT1R) is involved in the regulation of cardiovascular function. Excessive activation of AT1R by angiotensin II (Ang II) leads to cardiovascular disease and may be involved in the development of insulin resistance and diabetes. Functionally selective Ang II analogues, such as the [Sar1, Ile4, Ile8]-angiotensin II (SII Ang II) analogue that only activates a subset of signalling networks have been demonstrated to have beneficial effects on cardiovascular function in certain settings, including lowering blood pressure and increasing cardiac performance...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
F N Ramalho, S C Sanches, M C Foss, M J Augusto, D M Silva, A M Oliveira, L N Ramalho
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is highly associated with metabolic syndrome, a major cause of morbidity in the globalized society. The renin-angiotensin system (RAS) influences hepatic fatty acid metabolism, inflammation and fibrosis. Thus, in the present study, we aimed to evaluate the effect of aliskiren, a direct renin inhibitor, on metabolic syndrome-related NASH. METHODS: C57BL/6 male mice (n = 45) were divided into three groups: controls; animals inoculated with streptozotocin (STZ) (40 mg/kg/day) for 5 days and fed with high fat diet (HFD) for 8 weeks; and animals inoculated with STZ for 5 days, fed with HFD for 8 weeks and treated with aliskiren (100 mg/kg/day) for the final 2 weeks...
2017: Diabetology & Metabolic Syndrome
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