ABSTRACT
La insuficiencia cardíaca (IC) se define como la incapacidad del corazón de satisfacer los requerimientos metabólicos de los tejidos en reposo o durante el ejercicio ligero. Esta incapacidad motiva una respuesta neurohormonal que se interrelaciona con las alteraciones hemodinámicas vinculadas a las cargas ventriculares, más los problemas funcionales y estructurales del miocardio que puedan existir. En la fisiopatología cardiovascular (de la IC, de la hipertensión arterial, de las valvulopatías, de la enfermedad coronaria, etc.), tiene participación clave el sistema renina angiotensina (SRA), cuyas acciones principales incluyen la regulación de la presión arterial, el tono vascular, la volemia y facilitar la transmisión simpática. El SRA participa en la remodelación ventricular del infartado y del hipertenso, así como en la remodelación vascular. Esta revisión sobre algunos nuevos aspectos del SRA, publicados recientemente en la literatura médica, se acompaña de un resumen de los conceptos clásicos, para ver cómo los nuevos se instalan en ellos, se abren nuevos caminos en la investigación fisiológica y farmacológica, al ampliarse significativamente el espectro de acción del SRA, eje de la fisiopatología de la hipertensión arterial, de la insuficiencia cardíaca y de otras patologías.
Heart failure (HF) is defined as the inability of the heart to satisfy the metabolic requirements of the tissues at rest or during light exercise. This failure motivates neurohormonal response that interrelates with the hemodynamic changes related to ventricular loads more functional and myocardial structural problems that may exist. In cardiovascular pathophysiology (HF, arterial hypertension, valvular heart disease, coronary disease, etc.) has key role the renin angiotensin system (RAS), whose main activities include to regulate blood pressure, vascular tone, volemia and to facilitate sympathetic transmission. The RAS participates in ventricular remodeling of the infarcted and of the hypertensive as well as vascular remodeling. This review of some new aspects of the RAS, recently published in the medical literature, is accompanied by a summary of the classical concepts, to see how new they are installed, opening new pathways in physiological and pharmacological research, to significantly expand the RAS spectrum of action, axis of the pathophysiology of hypertension, heart failure and other diseases.
A insuficiência cardíaca (IC) é definida como a incapacidade do coração para atender às necessidades metabólicas dos tecidos em repouso ou durante exercícios leves. Esta falha motiva resposta neuro-hormonal que interage com as alterações hemodinâmicas relacionadas às cargas ventriculares mais os problemas funcionais e estruturais do miocárdio que possam existir. Na fisiopatologia cardiovascular (IC, hipertensão arterial, doença cardíaca valvular, doença coronariana, etc.) tem papel fundamental no sistema renina angiotensina (SRA), cujas ações principais incluem a regulação da pressão arterial, do tônus vascular, da volemia e facilitar a transmissão simpática. O SRA participa de remodelação ventricular do infartado e do hipertenso assim como a remodelação vascular. Esta revisão de alguns novos aspectos da SRA, recentemente publicado na literatura médica, é acompanhada por um resumo dos conceitos clássicos, para ver como novo eles estão instalados, abrindo novos caminhos na pesquisa fisiológica e farmacológica, para expandir de forma significativa a espectro de ação da SRA, eixo da fisiopatologia da hipertensão, insuficiência cardíaca e outras doenças.
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Objective To investigate the effect of chymase on the proliferation of rat cardiac fibroblasts (CFs) and the role of transforming growth factor-?1 (TGF-?_1).Methods Cultured CFs of neonatal SD rats were isolated by trypsinization.Cell number and DNA synthesis were evaluated by MTT assay (A_(490) value) and [~3H]-deoxythy- midine [~3H]-TdR incorporation.The mRNA expression of TGF-?_1 in CFs was determined by RT-PCR.Results Chymase increased CFs numbers and [~3H]-TdR incorporation in a dose-dependent manner.The A_(490) value of CFs stimulated by 15,30 and 60 ng/mL chymase was 0.263?0.033,0.348?0.031 and 0.387?0.026,respectively, which were all significantly higher than that of control (0.201?0.019,P
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Objective:To investigate the relationship of gene expression and activity of chymase and Ang Ⅱwith nephropathy in the streptozotocin(STZ)-induced diabetic hamsters.Methods:Thirty male hamsters were randomly divided into two groups:normal controls and diabetic rats.Diabetes mellitus was induced in rats by intraperitoneal streptozotocin injection.The nephritic ultrastructure was observed with electron microscope.The levels of blood glucose,lipoprotein were measured by biochemical methods.The level of angiotensin Ⅱ(Ang Ⅱ) and the activity of chymase and angiotensin-convertion enzyme(ACE) were measured by radioimmuno assay.Reverse transcription polymerase chain reaction(RT-PCR)was used to determine chymase gene expression(corrected by ?-actin).Results:Chymase activity in DN group was much higher than that in the control group(0.82?0.05) U vs(0.49?0.03) U,P
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Objective To explore how does chymase affect diabetic cardiomyopathy by investigating the gene expression of chymase and the relationship between the gene expression of chymase and the angiotensin Ⅱ in the cardiomyopathy of streptozotocin-induced diabetic hamasters. Methods Diabetic hamsters were induced by intraperitoneal injection of STZ 40 mg/kg once a day for 3 days. After stabilization of diabetic state for 18 weeks, the myocardial ultrastructure was observed with electron microscope and pathologic changes were observed by light microscopy. Immunohistochemistry was used to measure the level of expression of type Ⅰ and type Ⅲ collagen in diabetic and normal hamster hearts. Level of blood glucose, lipoprotein was determined using biocehemical methods. Apoptosis of cardiomyocyte was measured using TUNEL methods. Radioimmunuoassay method was used to determine the level of angiotensin Ⅱ. RT-PCR was used to determine chymase gene expression (corrected by?-actin). ResultsComparing with the control group, levels of serum glucose, TG, TC, LDL in DM group were much higher. Concentrations of collagen Ⅰ, Ⅲ and angiotensin Ⅱ [(95.8?16.0)?g/kg tissue vs (51.1?20.8)?g/kg tissue] in myocardial tissue in DM group were much higher than those in control group. RT-PCR result showed: Comparing with the control group, the mRNA expression of chymase in DM group was promoted significantly (0.810?0.026 vs 0.490?0.087). Conclusion In diabetic hamsters, the gene expression of chymase were much higher than thatin the control group, accompanying higher level of Angiotensin Ⅱ, higher levels of expression of collagen Ⅰ and Ⅲ. This result suggests that chymase plays an important role in the diabetic cardiomyopathy by promoting the activity of chymase.
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Objective: To investigate the mechanism of curative effects of Guben Fangchuan capsule (固本防喘胶囊) on chronic obstructive pulmonary disease(COPD). Methods: Using double blind control method , 86 elderly COPD patients in in acute exacerbating stage were divided into treatment group and control group (n=43 in each group). The conventional treatment of the two groups was the same. Additionally, the patients in the treatment group were given Guben Fangchuan capsules orally. The levels of interleukinCD*28 (ILCD*28) and eotaxin in phlegm were detected by enzyme linked immunoadsorbent assay (ELISA). Chymase activity in phlegm was determined by spectrophotometry. They were compared before and after treatment. Results: ①The activity of chymase, the levels of ILCD*28, eotaxin, neutrophil (NEU) and eosinophil (EOS) in phlegm in patients with intermediate and severe COPD patients were lower after treatment in treatment group than those of the patients before treatment and control group (all P
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Background Cardiac mast cell-derived chymase is involved in myocardial fibrosis,but the underlying mechanisms remain unclear. Objective To investigate the effect of chymase on the collagen synthesis and its relationship with transforming growth factor-?1 (TGF-?1)/Smad pathway in rat cardiac fibroblasts (CFs). Methods CFs,from neonatal SD rats,were isolated by trypsinization. The collagen synthesis of CFs was determined by 3H-proline incorporation. The protein expressions of TGF-?1,phosphorylated Smad2/3 (P-Smad2/3) and total Smad2/3 were determined by immunoblotting in CFs. Results Chymase (15,30 and 60 ?g/L) increased the 3H-proline incorporation in a concentration-dependent manner. 30 ?g/L chymase stimulation increased the protein expressions of TGF-?1 and P-Smad2/3 in a time-dependently,while little effect on Smad2/3 protein expression was found. The stimulatory effect of chymase on 3H-proline incorporation elicited by 30 ?g/L chymase was blocked in the presence of TGF-?1 antibody or staurosporine,a P-Smad2/3 inhibitor. Conclusion Chymase promotes collagen synthesis of rat CFs,TGF-?1/Smad might be involved into the signal pathway.
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Renin-angiotensin system (RAS) is correlative with many diseases. Angio tensin II (AngII) plays an important role as the final effective approach for RAS. This article reviews the main approach to the action and biosynthesis of AngII: including AngII receptor blocker (ARB), chymase inhibitor and ACE2 which were disscoverd recently.
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Aim To investigate the ability of chymase inhibitors o n histamine release from human colon mast cells. Methods Human ma st cells were dispersed from colon tissue with collagenase and hyaluronidase, an d were challenged with stimulus for 15 min at 37℃.A glass fibre-based fluorome tric assay was used to measure histamine in the supernatants of dispersed mast c ells.Results chymase inhibitors ZIGPFM, TPCK and ? 1-antitry psin failed to induce significant histamine release from colon mast cells. All t he chymase inhibitors were able to inhibit anti-IgE induced histamine release i n a concentration dependent manner with a maximum of 37%, 26% and 36.8% inhibit ion being achieved with 1 mmol?L -1 of ZIGPFM, 80 mmol?L -1 of TPCK , 30 mmol?L -1 of ? 1-antitrypsin, respectively. Preincubation of inhib itors of ZIGPFM and TPCK with cells for 20 min at 37℃ before challenging with a nti-IgE was able to slightly enhance their inhibitory actions. All the chymase inhibitors were able to inhibit calcium ionophore induced histamine release, th e maximum inhibition was 23.6%～35%.And the extent of inhibition by TPCK was in creased when colon mast cells were preincubated for 20 min before calcium ionoph ore being added. However, the same treament failed to improve the action of ZIGP FM. Conclusion In the current study, we found that inhibitors o f chymase were able to inhibit anti-IgE and calcium ionophore induced histamine release from human colon mast cells, which may indicate a potential of a novel therapy for the treatment of inflammatory bowel disease or other mast cell relat ed diseases.
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BACKGROUND: It has been suggested that mast cells are involved in the tumor growth and progression by production of a variety of enzymes and growth factors. They were studied in the 10-dimethyl-1,2 benzanthracene (DMBA)-induced rat mammary tumors, and evaluated in relation with the production of tryptase, chymase, and matrix metalloproteinase (MMP)-2 and MMP-9. METHODS: Preneoplastic and neoplastic breast tissues of Sprague-Dawley female rats were obtained every week after DMBA treatment for 12 weeks. Toluidine blue stain was used for the identification of mast cells. Mast cell tryptase was studied by immunohistochemistry, and chymase by esterase stain. MMP-2 and MMP-9 were measured by Western blotting. RESULTS: The numbers of mast cells in breast cancers were higher than in preneoplastic tissues, and there was a positive correlation between the numbers of tryptase-positive cells and the tumor size. MMP-9 quantity was correlated with the numbers of toluidine blue and chymase positive cells, but not with tryptase-positive cells and tumor size. Both active and inactive forms of MMP-2 and MMP-9 were identified in zymogram. CONCLUSIONS: The mast cells are increased in the DMBA-induced breast cancers, and their tryptase and chymase may play a role in tumor progression with or without participation of MMP-2 and MMP-9.
Subject(s)
Animals , Female , Humans , Rats , 9,10-Dimethyl-1,2-benzanthracene , Blotting, Western , Breast , Chymases , Immunohistochemistry , Intercellular Signaling Peptides and Proteins , Mast Cells , Rats, Sprague-Dawley , Tolonium Chloride , TryptasesABSTRACT
Objective:To investigate the ability of chymase inhibitors on tryptase release from human colon mast cells.Methods:Human mast cells were dispersed from colon tissue with collagenase and hyaluronidase,and were challenged with stimulus for 15 min at 37℃.Tryptase assay performed following previous procedures.In brief,a 96-well microtitre plate was coated with antiserum to human tryptase.The tryptase levels in the samples were detected with a monoclonal antibody specific to tryptase and the reaction was visualized by addition of OPD.Results:At 15 min and 35 min following incubation,anti-IgE and calcium ionophore were able to provoke significant tryptase release from human colon mast cells.Chymase inhibitors ZIGPFM,TPCK and ?1-antitrypsin had no stimulatory effect on colon mast cells at both 15 min and 35 min incubation periods.All the chymase inhibitors were able to inhibit anti-IgE induced tryptase release in a concentration dependent manner with a maximum of 37%,40% and 36.6% inhibition being achieved with 1 ?mol/mL of ZIGPFM,80 ?mol/mL of TPCK,30 ?mol/mL of ?1-antitrypsin,respectively.Preincubation of inhibitors of ZIGPFM and TPCK with cells for 20 min at 37℃ before challenging with anti-IgE was able to slightly enhance their inhibitory actions.Amastatin,a specific inhibitor of aminopeptidase,had no effect on anti-IgE induced tryptase release.All the chymase inhibitors were able to inhibit calcium ionophore induced tryptase release,the maximum inhibition were 23%-35.3%.And the extent of inhibition by ZIGPFM was increased when colon mast cells were preincubated for 20 min before calcium ionophore being added.However,the same treament failed to improve the action of TPCK.Conclusion:We found for the first time that inhibitors of chymase were able to inhibit anti-IgE and calcium ionophore induced tryptase release from human colon mast cells,which may indicated a potential of a novel therapy for the treatment of inflammatory bowel disease or other mast cell related diseases.
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AIM: To investigate the levels of IL-18, IL-16, IL-8, eotaxin and the chymase activity in the sputum of asthmatics. METHODS: IL-18, IL-16, IL-8 and eotaxin levels were detected with sandwich ELISA procedures and chymase activity was determined spectrophotometrically (410 nm) by the rate of hydrolysis of N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (SAAPP). RESULTS: The specific chymase activities in the severe and moderate asthmatics were higher than that in controls. Native protease inhibitors ?_1-antitrypsin (?_1-AT) and soybean trypsin inhibitor (SBTI) inhibited 71.9% and 72.1% enzymatic chymase activity, respectively. The levels of IL-18, IL-16, IL-8 and eotaxin were significantly elevated in the sputum of patients with acute asthma. There were correlations between the levels of IL-8 and IL-16 (r=0.55, P
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AIM To investigate the relationship between myocardium chymase like activity and cardiac hypertrophy. METHODS The model of pressure overload hypertrophy was eatablished in rats. The changes of the HW/BW and LVH/BW and myocardium chymase like activity were investigated in the two groups of rats. RESULTS In cardiac hypertrophic rats 2,6,12 weeks after operation,the HW/BW and LVH/BW and myocardium chymase like activity were all significantly increased ( P