Disease relevance of Cma1

• Angiotensin converting enzyme-independent angiotensin ii production by chymase is up-regulated in the ischemic kidney in renovascular hypertension [1].
• Plasma ANG II does not appear to regulate intrarenal chymase activity, suggesting that ischemia per se up-regulates chymase activity in the kidney [1].
• Chymase inhibition prevents cardiac fibrosis and dysfunction after myocardial infarction in rats [2].
• These findings demonstrate that it is possible to inhibit both cathepsin G and chymase with a single molecule and suggest an exciting opportunity in the treatment of asthma and chronic obstructive pulmonary disease [3].
• The effect of mast cell chymase on extracellular matrix: studies in autoimmune thyroiditis and in cultured thyroid cells [4].

High impact information on Cma1

• Preparative purification of the rat mast cell chymase: characterization and interaction with granule components [5].
• Ligand 1 occupies the S(1) and S(2) subsites of cathepsin G and chymase similarly, with the 2-naphthyl in S(1), the 1-naphthyl in S(2), and the phosphonate group in a complex network of hydrogen bonds [3].
• In contrast, efflux of free cholesterol from Fu5AH to chymase-treated and to untreated HDL(3) was similar [6].
• Chymase, a protease secreted by mast cells, selectively cleaves pre-beta-migrating particles from high density lipoprotein (HDL)(3) and reduces the efflux of cholesterol from macrophages [6].
• Hence, the extended substrate specificity is similar to human chymase in most positions except for the P1 position [7].

Chemical compound and disease context of Cma1

• One day after the ligation, rats were randomized into 2 groups: 1) a chymase-treated group that received 10 mg/kg per day of the chymase inhibitor NK3201 orally for 4 weeks; and 2) a vehicle group of non-treated rats with myocardial infarction [2].
• Administration of tranilast to diabetic rats reduced mesenteric vessel fibrosis and this was associated with a reduction in chymase-positive mast cells [8].

Biological context of Cma1

• When the deduced amino acid sequence was compared with those of other known mast-cell proteinases, rMCP-3 was considered to be translated as a preproenzyme with a 19-amino-acid signal peptide, a two-amino-acid activation peptide and a 226-amino-acid mature enzyme [9].
• Sodium orthovanadate, an inhibitor of tyrosine phosphatases, inhibited the chymase-induced SMC apoptosis [10].
• These observations indicate that nonadditive interactions between the extended substrate binding site of human chymase or rat chymase-1 and the substrate are best explained if the entire binding site is taken as an entity rather than as a collection of distinct subsites [11].
• RESULTS: A model of transgenic mice with selective overexpression of a rat myosin light chain 2 promoter-human heart chymase (MLC(2-)-hChymase) fusion gene was produced [12].
• The results also suggest that chymase may play a role in heart remodeling by increasing Ang II formation and activating MMP-9, and the regulation of collagen I gene expression [12].

Anatomical context of Cma1

• Extended substrate specificity of rat mast cell protease 5, a rodent alpha-chymase with elastase-like primary specificity [7].
• While the expression of rMCP-1 and rMCP-2 are clearly restricted in connective-tissue mast cells and mucosal mast cells respectively, rMCP-3 was widely expressed in both types of mast cells with a predominance in connective-tissue mast cells [9].
• OBJECTIVE: Chymase released from activated mast cells has been shown to induce apoptosis of vascular smooth muscle cells (SMCs) in vitro [10].
• Mast cell chymase induces smooth muscle cell apoptosis by a mechanism involving fibronectin degradation and disruption of focal adhesions [10].
• Angiotensin II-forming chymase is expressed in the pulmonary arteries of the monocrotaline-induced pulmonary hypertensive rats, but its actual role is unclear [13].

Associations of Cma1 with chemical compounds

• Moreover, we focused on the role of chymases, which exhibit proinflammatory and pro-angiogenic properties by using: (i) chymostatin, an inhibitor of chymase activity; (ii) a specific antisense oligonucleotide (AS-ODN) designed against rat mast cell protease-5 (rMCP-5), the most abundantly expressed chymase in the skin [14].
• Distinct multisite synergistic interactions determine substrate specificities of human chymase and rat chymase-1 for angiotensin II formation and degradation [11].
• CONCLUSIONS: We have demonstrated selective overexpression of human chymase gene in the heart of transgenic mice, and the results support the hypothesis of a dual Ang II-forming pathway from chymase and ACE in the cardiac tissue in vivo [12].
• Cell association of complexes of chymase, heparin proteoglycan, and protein after degranulation by rat mast cells [15].
• With incremental concentrations of chymase, the release of granule markers occurred with a shorter lag period and in a greater maximal net percent, whereas the release of PGD2 was dose-related without a reduction in latency to detectable generation [16].

Other interactions of Cma1

• In other species (rat, bovine and porcine), the level of chymase as well as total Ang II-forming activities in pineal glands were significantly lower than those in human glands [17].
• The expression of chymase 1 in heart was higher than that of chymase 2 [18].

Analytical, diagnostic and therapeutic context of Cma1

• The chymase mRNA levels in the heart and other tissues were assessed by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) [12].
• Chymase and angiotensin-converting enzyme (ACE) activities, and angiotensin II (Ang II) content in the heart were determined by radioimmunoassay (RIA) [12].
• Four weeks after ligation, echocardiography revealed that chymase inhibitor treatment reduced the akinetic area and increased fractional area change but did not significantly change left ventricular end-diastolic area [2].
• We show here by means of RT-PCR, immunoblotting, and immunocytochemistry that isolated rat peritoneal mast cells synthesize and store large latent TGF-beta1 in their chymase 1-containing secretory granules [19].
• METHODS: The gene organization and the primary structure of hamster chymase were determined through molecular cloning [20].

References