Roles of chymase in the development of cardiac remodeling during heart failure progression.

肥大细胞源性糜酶在血管紧张素Ⅱ（angiotensin，Ang Ⅱ）的生成过程中起重要作用。除了生成血管紧张素II的特性外，最近的研究证实，糜酶还参与将潜在的转化生长因子β 1（TGF-β 1）切割成活性形式。这些结果表明，在病理条件下，食糜可能作为纤维化促进因子促进各种器官的重塑。为了验证这一假设，我们从狗舌中纯化了糜酶，并将其注入大鼠肝脏。与生理盐水注射相比，注射纯化的狗糜酶后纤维化面积显著增大，并且当糜酶在100 ℃下加热5分钟时，纤维化面积几乎减小到生理盐水注射的水平。有趣的是，我们发现糜酶注射的纤维化作用是浓度和时间依赖性的。这些发现直接表明， ...更多信息 糜蛋白酶的增加确实加速了纤维化过程，尽管尚不清楚在注射糜蛋白酶后Ang II生成特性和潜在的TGF-α α 1活化之间的这些过程中哪种途径更重要。为了进一步证实这一问题，糜酶抑制剂和血管紧张素II受体拮抗剂以及糜酶抑制剂与血管紧张素II受体拮抗剂的组合的影响正在进行中的同一model.The糜酶在心脏肥大和心肌病的发展过程中的作用也确定在仓鼠模型的腹部动静脉（AV）瘘和采用自发性心肌病仓鼠。在这些模型中，我们的免疫组化研究综述了糜酶阳性肥大细胞的大量沉积总是伴随着明显的局灶性纤维化军团，并且与年龄匹配的正常对照组相比，这些疾病心脏中的糜酶酶活性也显著增加。在不久的将来，糜酶抑制和血管紧张素II阻断以及它们的组合的效果将是明显的。少

It is well known that the mast cell derived chymase plays an important role in the generation of angiotensin (Ang) II form Ang II. In addition to its Ang II generation property, the recent studies confirmed that chymase also participate in the cleavage of latent transforming growth factor-beta 1 (TGF-ss1) to the active forms. Taking together, these results indicating that chymae may act as a fibrogenic facilitating factor to promote various organs remodeling during pathological conditions. To verify our this hypothesis, we have purified chymase from dog tongue, and injected it into the rat liver. In comparison with saline injection, the fibrotic area was significantly large after injection of the purified dog chymase and the fibrotic area was almost reduced to the saline injected level when the chymase was heated at 100 ℃ for 5 minutes. Interestingly, we found that the fibrogenic effect of chymase injection was concentration- and time-dependent. These findings direct demonstrated that … More the increase of chymase indeed accelerating fibrogenic processes, although it was unclear which pathway will be more important during these processes between Ang II-generating property and latent TGF-aa1 activation after injection of the chymase. To further confirm this issue, the effects of a chymase inhibitor and an Ang II receptor antagonist as well as a chymase inhibitor combined with an Ang II receptor antagonist are ongoing in the same model.The roles of chymase during the development of cardiac hypertrophy and cardiomyopathy were also determined in a hamster model of abdominal arteriovenous (AV) fistula and by employing spontaneous cardiomyopathy hamsters. In these models, our immunohistochemical studies reviewed that the great deposition of chymase positive mast cells always accompanied the significant focal fibrotic legion, and the enzymetic activities of chymase in the disordered hearts were also increased significantly when these compared to the age-matched control normal heats. The effects of chymase inhibition and Ang II blockade as well as their combination to be pronounced in the near future. Less