Chymase is responsible for the formation of
angiotensin II, which plays crucial roles in the pathogenesis of
cardiovascular diseases. In the present study we determined the gene organization of a novel hamster
chymase (hamster
chymase 2) and analysed the expression of
chymase 1,
chymase 2 and
angiotensin-converting enzyme (ACE) in hamster hearts at the terminal stage of
cardiomyopathy. The gene encoding hamster
chymase 2 is 3.2 kb in length and has five exons and four intervening sequences. The overall organization of this gene is similar to that of several other
serine proteases. The deduced amino acid sequence revealed the existence of a preproenzyme composed of a
signal peptide with 19
amino acids, a propeptide with two
amino acids and a catalytic domain with 226
amino acids. The predicted full sequence of the catalytic domain was revealed to be very similar to the sequences of
mouse mast-cell protease 5 (86%), rat mast-cell
protease III (85%) and human
chymase (70%) and less similar to hamster
chymase 1 (56%). The expression of
chymase 1 in heart was higher than that of
chymase 2. The cardiac
chymase-like activity, as well as the
mRNA levels of
chymase 1 and 2 of BIO 14.6 cardiomyopathic hamsters at the age of 60 weeks were increased 3.4-, 2.8- and 5.1-fold respectively compared with age-matched BIO F1B control hamsters. The cardiac ACE activity and the ACE
mRNA level of cardiomyopathic hamsters were also increased 4.1- and 2.4-fold compared with those of age-matched controls. These results suggest that up-regulation of both ACE and
chymases participates in the pathophysiology of the terminal stage of
cardiomyopathy.