Plasma cathepsin D isoforms and their active metabolites increase after myocardial infarction and contribute to plasma renin activity

R. Harris Naseem, Wade Hedegard, Timothy D. Henry, Jennifer Lessard, Kathryn Sutter, Stephen A. Katz

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Plasma renin activity (PRA) is often found to increase after myocardial infarction (MI). Elevated PRA may contribute to increased myocardial angiotensin II that is responsible for maladaptive remodeling of the myocardium after MI. We hypothesized that MI would also result in cardiac release of cathepsin D, a ubiquitous lysosomal enzyme with high renin sequence homology. Cathepsin D release from damaged myocardial tissue could contribute to angiotensin formation by acting as an enzymatic alternate to renin. We assessed circulating renin and cathepsin D from both control and MI patient plasma (7-20 hours after MI) using shallow gradient focusing that allowed for independent measurement of both enzymes. Cathepsin D was increased significantly in the plasma after MI (P < 0.001). Furthermore, circulating active cathepsin D metabolites were also significantly elevated after MI (P < 0.04), and contained the majority of cathepsin D activity in plasma. Spiking control plasma with cathepsin D resulted in a variable but significant (P = 0.005) increase in PRA using a clinical assay. We conclude that 7-20 hours after MI, plasma cathepsin D is significantly elevated and most of the active enzymatic activity is circulating as plasma metabolites. Circulating cathepsin D can falsely increase clinical PRA determinations, and may also provide an alternative angiotensin formation pathway after MI.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalBasic Research in Cardiology
Volume100
Issue number2
DOIs
StatePublished - Mar 1 2005

Keywords

  • Cathepsin D
  • Myocardial infarction
  • Renin-angiotensin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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