• Thus, mast cells are the source of the vascular ACE-independent pathway, and the antihypertensive benefit of combining ACE inhibitor therapy with AT(1) receptor antagonist therapy is most likely due to negation of chymase-catalyzed Ang II generation. (nih.gov)
  • Balloon injury remarkably activated canine vascular chymase, 10 and an ANG II receptor antagonist substantially prevented neointima formation, whereas an ACE inhibitor did so only modestly. (ahajournals.org)
  • RWJ-355871) as a novel, potent dual inhibitor of neutrophil cathepsin G (K(i) = 38 nm) and mast cell chymase (K(i) = 2.3 nm). (rcsb.org)
  • Separately, rat myocardial fibroblast was incubated with vehicle ( n = 4), low-dose chymase ( n = 4), high-dose chymase ( n = 4), or high-dose chymase plus chymase inhibitor ( n = 4). (aspetjournals.org)
  • molecular weight 526.60), a specific chymase inhibitor (CM), on a clinically relevant swine model of AMI-R. A 60-min ischemia followed by a 120-min reperfusion was chosen to assess an early effect of chymase inhibition (it is the shorter time point where necrosis can be determined with accuracy and reproducibility) and to allow comparison with previous experiments performed by our group. (aspetjournals.org)
  • The specific chymase inhibitor TY51469 was synthesized at Toa Eiyo Ltd. (Tokyo, Japan). (aspetjournals.org)
  • Chymase inhibitor drugs would work by allowing IGF-1, produced by the injured heart, to last longer. (emory.edu)
  • A clinical trial using a chymase inhibitor in heart failure patients is underway in Europe. (emory.edu)
  • Because lethal arrhythmias are generally believed to contribute to sudden cardiac death, we assessed whether inhibition of cardiac chymase would provide an antiarrhythmic effect during the 8-h ischemic period after 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamide-3-methanesulfonylphenyl]oxazole-4-carboxylicacid (TY51184) (a specific chymase inhibitor, 1 mg/kg i.v.) treatment by ligation of left anterior descending coronary artery (LAD) in dogs. (spotidoc.com)
  • Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR. (lvhn.org)
  • A decreased cholesterol efflux to untreated HDL3 but not to chymase-treated HDL3 was observed in ABCA1-expressing J774 with probucol, an inhibitor of cholesterol efflux to lipid-poor apoA-I. Similar results were obtained using brefeldin and gliburide, two inhibitors of ABCA1-mediated efflux. (unimi.it)
  • 15 These results indicate that chymase contributes to the pathogenesis of intimal hyperplasia by augmenting the local ANG II production to a greater extent than does ACE. (ahajournals.org)
  • These results indicate that chymase treatment of HDL3 specifically impairs the ABCA1-dependent pathway without influencing either aqueous or SR-BI-facilitated diffusion and that this effect is caused by depletion of lipid-poor pre-β-migrating particles in HDL3. (unimi.it)
  • Nevertheless, it remained to be determined whether these immune cells could modify their expression of other chymases and the granule tryptases mMCP-6 and mMCP-7. (jimmunol.org)
  • Here we show that the predominant chymase mRNA species in the mouse aorta are those for types 4 and 5 isoforms, and that both are efficient Ang II-forming enzymes. (nih.gov)
  • 7 8 9 10 11 Chymases of these species cleave the Phe 8 -His 9 bond of ANG I and produce ANG II efficiently. (ahajournals.org)
  • To better understand mast cell functions in these species, one member of the mouse Mcpt8-family, mMCP-8, and human and dog chymase were studied. (diva-portal.org)
  • Suppression of the chymase-dependent ANG II-forming pathway may contribute to the beneficial effects of tranilast. (ahajournals.org)
  • This study demonstrates that chymase inhibition plays crucial roles in myocardial protection related to MMP-9, inflammatory markers, and the eNOS pathway. (aspetjournals.org)
  • In contrast, rats possess only an ACE-dependent Ang II-forming pathway, because in cardiovascular tissues in rat, chymase acts as an This study was supported by Grant-in-Aid 13670102 (C) for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan. (spotidoc.com)
  • Evaluation of ACE-dependent and ACE-independent Ang II-forming pathways in mast cell-deficient (Kit(w)/Kit(w-v)) mice and their mast cell-sufficient littermate (MC(+/+)) controls revealed that, in contrast to the latter, Kit(w)/Kit(w-v) mice fail to express chymase mRNAs in the vasculature and have almost no ACE-independent Ang II-forming activity in either isolated blood vessels or homogenates. (nih.gov)
  • 2001, 2002, 2003), which possesses both chymase and ACE-dependent Ang II-forming pathways like in humans, as mentioned above. (spotidoc.com)
  • Studies of the mast cell chymase locus are therefore important to better understand the mammalian immune system. (diva-portal.org)
  • In this thesis, the evolution of the mast cell chymase locus was analysed by mapping the locus in all available mammalian genome sequences. (diva-portal.org)
  • Therefore, together with the rat chymase (rMCP1), sheep MCP2 can be grouped to a small subfamily of mammalian chymases that show fairly unspecific preference in the P2′position. (usda.gov)
  • GAPDH-normalized chymase 1, chymase 2, chymase 4, and chymase 5 mRNA levels in aortae from vehicle- or captopril-treated MC +/+ and Kit w /Kit w-v mice. (nih.gov)
  • Chymase mRNA levels and chymaselike activity of vehicle-treated injured arteries were increased 10.2- and 4.8-fold, respectively, those of uninjured arteries. (ahajournals.org)
  • Recombinant protein encompassing a sequence within the center region of human Mast Cell Chymase. (genetex.com)
  • Purified human skin chymase. (genetex.com)
  • Previously we demonstrated that chymase contributed to ANG II formation in human, monkey, and dog vascular tissues. (ahajournals.org)
  • The original objectives of the project was 1) to develop Westernblot analysis and biochemical assay for plasma human chymase, 2) to determine clinical significance of plasma chymase measurement, 3) to develop RIA method for human chymase to handle massive clinical samples, 4) to compare plasma chymase levels in various cardiovascular diseases, 5) to determine the association between plasma chymase level and various cardiovascular diseases. (nii.ac.jp)
  • Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta'Hypertension. (nii.ac.jp)
  • Human mast cell chymase cleaves angiotensin I selectively at Phe 8 to generate bioactive angiotensin II ( 1 , 2 , 3 , 4 ). (jimmunol.org)
  • However, subsequent work revealed that serpins, including α 1 -antichymotrypsin (α 1 ACT), are better substrates for human chymase than they are inactivators, and that much or most of chymase added to serum is inactivated by α 2 -macroglobulin (α 2 M), with which the association rate constants are highly favorable ( 7 ). (jimmunol.org)
  • Human mast cells are classified into two groups: tryptase- and chymase-positive mast cells, and tryptase-positive and chymase-negative mast cells. (molvis.org)
  • Rat and mouse mast cells express numerous different graspases, whereas human and dog mast cells express only one graspase, chymase. (diva-portal.org)
  • In an extract of human heart tissues, for example, it was reported that chymase accounts for 80 to 90% of Ang II formation (Urata et al. (spotidoc.com)
  • In contrast to the human, mouse, hamster and opossum chymases that show a relatively strong preference for negatively charged amino acids in the P2′position, the sheep MCP2, however, lacked that preference. (usda.gov)
  • The amino acid sequence of human skin chymase was established by protein methods and by analysis of PCR amplification products obtained with cDNA-derived from urticaria pigmentosa (UP) lesions. (duke.edu)
  • Proteolytic digests of human chymase purified from normal skin yielded 10 resolvable peptides that were sequenced by automated Edman degradation. (duke.edu)
  • The amino acid sequences for these peptides combined with the sequence obtained for the protein's NH2-terminal region (35 residues) accounted for 137 residues of the human skin chymase sequence. (duke.edu)
  • This partial amino acid sequence corresponded to the sequence of human heart chymase, a proteinase isolated from heart tissue with immunologic and hydrolytic properties similar to skin chymase. (duke.edu)
  • This sequence, along with that established for the purified protein, constituted 99% of the heart chymase primary structure, strongly indicating that human skin and heart chymases have identical primary structures. (duke.edu)
  • Treatment of HDL3 with the human chymase resulted in rapid depletion of pre-β-HDL and a concomitant decrease in the efflux of cholesterol and phospholipid (2-fold and 3-fold, respectively) from the ABCA1-expressing J774 cells. (unimi.it)
  • 1993). "Reaction of human chymase with reactive site variants of alpha 1-antichymotrypsin. (wikipedia.org)
  • Crystal structure of phenylmethanesulfonyl fluoride-treated human chymase at 1.9 A". Biochemistry. (wikipedia.org)
  • These findings demonstrate that chymase inhibition can provide an antiarrhythmic effect after MI, and the reduction of Ang II by TY51184 may be mainly responsible for this beneficial effect. (spotidoc.com)
  • Chymase Inhibition Prevents Fibronectin and Myofibrillar Loss and Impr" by Betty Pat, Yuanwen Chen et al. (lvhn.org)
  • Chymase Inhibition Prevents Fibronectin and Myofibrillar Loss and Improves Cardiomyocyte Function and LV Torsion Angle in Dogs with Isolated Mitral Regurgitation. (lvhn.org)
  • These findings indicate that all chymase locus genes are derived from a single ancestor that was present more than 200 million years ago. (diva-portal.org)
  • Our findings show that a substantial level of heart muscle cell death occurs few days later, and its prevention by suppressing chymase activity could dramatically improve outcomes. (emory.edu)
  • There was a significant positive correlation between plasma chymase level and plasma c-reactive protein or fibrinogen. (nii.ac.jp)
  • Sections of concurrently obtained endobronchial and transbronchial/surgical biopsy tissue from 20 individuals with severe asthma were immunostained for T-lymphocyte, eosinophil, monocyte/macrophage, neutrophil, and two mast cell markers (tryptase and chymase). (nih.gov)
  • After the analysis was adjusted for multiple comparisons, only chymase-positive mast cells significantly and positively correlated with lung function. (nih.gov)
  • Plasma chymase levels significantly increased in systemic inflammatory diseases (pneumonia autoimmune disease and etc. (nii.ac.jp)
  • Densities of proliferative cell nuclear antigen-positive cells, chymase-positive cells, and areas of collagen fiber in conjunctival and scleral lesions were significantly decreased in MMC-treated eyes, compared with placebo-treated eyes (p=0.034, 0.034, 0.049, respectively). (molvis.org)
  • Total Ang II-forming activity and chymase activity in the infarcted heart were increased significantly 8 h after LAD ligation. (spotidoc.com)
  • In contrast, mast cell number, percentage, and the chymase-positive phenotype increased in small airway regions. (nih.gov)
  • In contrast, efflux of free cholesterol from Fu5AH to chymase-treated and to untreated HDL 3 was similar. (unimi.it)
  • We have assessed inhibitory effects of tranilast on neointima formation after balloon injury in the carotid artery of dogs, which share a similar ANG II-forming chymase with humans, and further explored the pathophysiological significance of vascular chymase. (ahajournals.org)
  • Dogs, like humans, have only one chymase. (diva-portal.org)
  • PCR amplification of UP-derived cDNA with primers based on the cDNA structure of heart chymase demonstrated a single amplification product of expected size which was subcloned and sequenced. (duke.edu)
  • This fact suggests that plasma chymase level may reflect the levels of tissue inflammation. (nii.ac.jp)
  • Detection of chymase activity using a specific peptide probe conjugated onto gold nanoparticles. (genetex.com)
  • Increased chymase activity in internal thoracic artery of patients with hypercholesterolemia'Hypertension. (nii.ac.jp)
  • The present work shows that α 2 -macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. (jimmunol.org)
  • The assay detects activity in chymase-spiked serum with a threshold of ∼1 pM (30 pg/ml), and reveals native chymase activity in serum of most subjects with systemic mastocytosis. (jimmunol.org)
  • Histochemical analysis of the spinotrapezius muscle reveals abundant perivascular mast cells with chymostatin-inhibitable chymase-like activity. (aspetjournals.org)
  • We speculate that activation of endothelial CLP/chymase may directly relate to the increased inflammatory phenotypic changes in the vascular system in women with PE. (preeclampsia.org)
  • For example, chymases are released by mucosal mast cells upon challenge with parasites and parasite antigens promoting an inflammatory response. (wikipedia.org)
  • 490 Downloaded from jpet.aspetjournals.org by guest on June 9, 2014 ABSTRACT Chymase plays an important role in the regulation of local angiotensin (Ang) II formation in the cardiac tissue. (spotidoc.com)
  • We used α 2 -macroglobulin capture to develop a sensitive, microtiter plate-based assay for serum chymase, assisted by a novel substrate synthesized based on results of combinatorial screening of peptide substrates. (jimmunol.org)