Is chymase 1 a therapeutic target in cardiovascular disease?

ABSTRACT

Introduction

Non-angiotensin converting enzyme mechanisms of angiotensin II production remain underappreciated in part due to the success of current therapies to ameliorate the impact of primary hypertension and atherosclerotic diseases of the heart and the blood vessels. This review scrutinize the current literature to highlight chymase role as a critical participant in the pathogenesis of cardiovascular disease and heart failure.

Areas covered

We review the contemporaneous understanding of circulating and tissue biotransformation mechanisms of the angiotensins focusing on the role of chymase as an alternate tissue generating pathway for angiotensin II pathological mechanisms of action.

Expert opinion

While robust literature documents the singularity of chymase as an angiotensin II-forming enzyme, particularly when angiotensin converting enzyme is inhibited, this knowledge has not been fully recognized to clinical medicine. This review discusses the limitations of clinical trials’ that explored the benefits of chymase inhibition in accounting for the failure to duplicate in humans what has been demonstrated in experimental animals.

KEYWORDS:

• Angiotensin converting enzyme
• angiotensin-(1-12)
• chronic kidney disease
• chymase
• diabetes mellitus
• heart failure
• primary hypertension
• vascular disease

Article highlights

• The therapeutic potential of chymase in the treatment of cardiovascular disease remains to be appreciated.

• Chymase represents an important enzymatic mechanism for the formation of Ang II from either Ang-(1–12) or Ang I.

• Chymase has multiple substrates other than angiotensins, the metabolism of which is predominantly detrimental.

• As a member of the serine protease family, chymase can be inhibited by many serine protease inhibitors.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by grant 1 R21 AG070371-01 (CM Ferrario) from the National Institutes of Health, Bethesda, MD.