Function of chymase in the heart angiotensin II formation in transgenic mice
The myosin light chain 2 promoter-human heart chymase (MLC2-hChymase) transgenic mice founded by our laboratory were used as the model to study the function of chymase in the heart angiotension II (Ang II) formation and heart remodeling. Tissue-specific expression of human heart chymase gene and transcriptional expression of type I and type HI collagens genes were analyzed by RT-PCR. Activities of chymase, ACE and the levels of Ang II in heart and plasma were determined with radioimmunoassay (RIA) kit. Activity of heart matrix metalloproteinase-9 (MMP-9) was detected using gelatin zymography. The cardiac hypertrophic phenotypes were also observed with the physiological and morphological methods. The results in the MLC2-hChymase transgenic mice indicated: (i) human heart chymase gene was expressed specially in the heart; (ii) heart chymase activity increased markedly in the transgenic mice vs non-transgenic mice (control) (0.27±0.07 U/mg vs. 0.15±0.02 U/mg,P< 0.05) with no significant difference in ACE activity (0.17±0.03 U/mg vs. 0.18±0.02 U/mg); (iii) heart Ang II content increased 3-fold (1984±184 vs. 568±88 pg/g protein,P< 0.05) but was unchanged in plasma (218 ±106 vs. 234 ±66 pg/mL); (iv) both MMP-9 activity and collagen I mRNA level increased significantly in the heart (P< 0.05) but there was neither significant increase in collagen El mRNA nor in the ratio of I / III collagen mRNA levels; (v) the MLC2-hChymase transgenic mice showed no significant changes in blood pressure, heart-rate, ratio of heart/body weight and cardiomyocyte diameter compared to the control. This suggests that heart Ang II formation catalyzed through overexpression of human heart chymase gene in the heart of transgenic mice might activate MMP-9 to influence collagen metabolism in cardiac interstitial and to be involved in the process of heart remodeling.
Keywordschymase transgenic mice angiotensin II heart remodeling collagen
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