The relationship between mast cells and fibrosis has been demonstrated. 25, -27 Regarding the underlying mechanisms, mast cells store and release several products capable of activating matrix metalloproteinases. Chymotrypsin plays a key role because it contributes to the activation of TGF-β, which is released from potential TGF-β-binding proteins in fibroblasts. Potential TGF-β-binding proteins are cleaved to form potential TGF-β. Taipale et al. proposed that rat chymotrypsin may contribute to the release of potential TGF-β from potential TGF-β-binding proteins in the extracellular matrix of epithelial and endothelial cells. 

In cultured human fibroblasts, chymotrypsin was found to significantly increase cell proliferation in fibroblasts. This increased cell proliferation is completely inhibited by chymotrypsin inhibitors, but not by Ang II receptor antagonists. 

In the medium supernatant of cultured fibroblasts, although TGF-β levels were significantly increased after chymotrypsin injection, this increase was inhibited by chymotrypsin inhibitors. Anti-tgf-β neutralizing antibodies completely inhibited human chymotrypsin-induced cell proliferation, suggesting that chymotrypsin may be a rate-limiting enzyme that activates TGF-β in vitro. These studies suggest that QLQX may act through the chymotrypsin TGF-β pathway.

In our current study, QLQX (Qiliqiangxin ingredients) significantly reduced gene expression and enzyme activity of local myocardial chymase in SHR, in addition to reducing local myocardial Ang II levels. However, the expression and activity of ACE in local cardiomyocytes did not change after QLQX treatment. 

Compared with excipient-treated rats, QLQX inhibited type I and III collagen and TGF-βmRNA levels in a dose-dependent manner and reduced LV fibrosis. Our results suggest that the beneficial effect of QLQX in the treatment of hypertensive cardiomyopathy is mainly due to the inhibition of local chymase-dependent TGF-β and Ang II formation pathways.