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(Circulation. 2003;107:2522.)
© 2003 American Heart Association, Inc.

Editorial

Role For Chymase in Heart Failure

Angiotensin II-Dependent or -Independent Mechanisms?

Jorma O. Kokkonen, MD, PhD; Ken A. Lindstedt, PhD; Petri T. Kovanen, MD, PhD

From the Wihuri Research Institute and the Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.

Correspondence to Petri T. Kovanen, Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, Finland. E-mail petri.kovanen@wri.fi

Key Words: Editorials • heart failure • angiotensin

An extract of the first 250 words of the full text is provided, because this article has no abstract.

One of the major questions regarding the role of angiotensin II (Ang II) in the pathophysiology of heart failure has been whether other enzymes, in addition to angiotensin-converting enzyme (ACE), could contribute to the local production of Ang II in the heart. Specifically, there is controversy as to whether the major Ang II-forming enzyme within the heart is ACE or chymase, a chymotrypsin-like serine protease that is synthesized and stored in the cardiac mast cells and is not affected by ACE inhibitors.

See p 2555

Formation of Ang II in the heart has been studied both in vitro and in vivo, but the results of these experiments are inconsistent. In vitro experiments with human^1,2 or animal heart extracts,^3,4 derived from either normal or failing hearts, have demonstrated unequivocally that the major Ang II-forming enzyme, responsible for 80% to 90% of the Ang II-forming capacity in the heart extracts, is chymase.

In striking contrast, experiments in vivo with normal^5,6 or failing dog hearts^7,8 have demonstrated that most (>70%) of the Ang II formation can be inhibited by an ACE inhibitor, indicating that, under these conditions, the major Ang II-forming enzyme is ACE. Moreover, in normal human hearts, Zisman et al⁹ have demonstrated that, in vivo, the major Ang II-forming enzyme is ACE, as 90% of the Ang II formation could be inhibited by an ACE inhibitor. However, no experiments with intact failing human hearts have been performed.

The obvious explanation for the discrepancy between the in vitro and in vivo studies . . . [Full Text of this Article]

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Chymase Inhibition Prevents Cardiac Fibrosis and Improves Diastolic Dysfunction in the Progression of Heart Failure

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Circulation 2003 107: 2555-2558. [Abstract] [Full Text]

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