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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-1-19
pubmed:abstractText
The enzymatic pathways for local angiotensin II (Ang II) formation in the heart have been studied both in vivo and in vitro, but the results of these experiments have been discrepant. Thus, the experiments in vivo with intact hearts, both in humans and in animal models, have unequivocally demonstrated that the major Ang II-forming enzyme is angiotensin-converting enzyme (ACE). In contrast, the experiments in vitro with both human or animal heart preparations, have unequivocally demonstrated that the major Ang II-forming enzyme is chymase, a mast cell-derived chymotrypsin-like serine protease. The in vitro approach, however, seems to involve several pitfalls, which tend to overestimate the contribution of chymase as compared to that of ACE. It seems evident that in vivo the chymase-mediated Ang II formation is subjected to local inhibition, a fact that has been overlooked in most of the studies performed in vitro. Accordingly, human chymase, even in its natural form as a protease-proteoglycan complex, is highly sensitive to the protease inhibitors naturally present in the interstitial fluid (IF). We found that if human heart tissue preparations are incubated in vitro in the presence of IF, the chymase-mediated Ang II formation is almost totally suppressed. As the heart interstitium is constantly bathed by IF with its protease inhibitors in concentrations sufficiently high to ensure efficient inhibition of this enzyme, the protease inhibitor-mediated suppression of chymase should also be effective in vivo. Thus, the local production of Ang II in the human heart appears to be regulated by ACE rather than by chymase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0785-3890
pubmed:author
pubmed:issnType
Print
pubmed:volume
30 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9-13
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Angiotensin II formation in the human heart: an ACE or non-ACE-mediated pathway?
pubmed:affiliation
Wihuri Research Institute, Helsinki, Finland. jorma.kokkonen@pp.fimnet.fi
pubmed:publicationType
Journal Article, In Vitro, Review, Research Support, Non-U.S. Gov't