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The Journal of Applied Laboratory Medicine

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Research ArticleFocused Reports

Proteolytic Digestion of Serum Cardiac Troponin I as Marker of Ischemic Severity

Somaya Zahran, Vivian P. Figueiredo, Michelle M. Graham, Richard Schulz, Peter M. Hwang
DOI: 10.1373/jalm.2017.025254 Published October 2018
Somaya Zahran
Department of Medicine, University of Alberta, Edmonton, AB, Canada;
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Vivian P. Figueiredo
Departments of Pediatrics and Pharmacology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada;
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Michelle M. Graham
Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada;
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Richard Schulz
Departments of Pediatrics and Pharmacology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada;
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Peter M. Hwang
Division of General Internal Medicine, Department of Medicine and Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
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  • For correspondence: phwang1@ualberta.ca
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Abstract

Background: The serum troponin assay is the biochemical gold standard for detecting myocardial infarction (MI). A major diagnostic issue is that some believe troponin levels can rise with reversible injury, in the absence of radiologically detectable infarct.

Hypothesis: Because cell death activates intracellular proteases, troponin released by irreversible infarct will be more proteolyzed than that released by milder processes. Our goal was to quantify proteolytic digestion of cardiac troponin I in patients with varying degrees of myocardial injury.

Methods: Serum or plasma samples from 29 patients with cardiac troponin I elevations were analyzed for proteolytic degradation, using 3 different sandwich ELISAs designed to specifically detect the N-terminal, core, or C-terminal regions of cardiac troponin I.

Results: As predicted, the degree of proteolytic digestion increased with increasing severity of injury, as estimated by the total troponin level, and this trend was more pronounced for C-terminal (vs N-terminal) degradation. The highest degree of proteolytic digestion was observed in patients with ST-elevation MI; the least, in type 2 MI (supply–demand ischemia rather than acute thrombus formation).

Conclusions: The proteolytic degradation pattern of cardiac troponin I may be a better indicator of clinically significant MI than total serum troponin level. Distinguishing between intact and degraded forms of troponin may be useful for (a) identifying those patients with clinically significant infarct in need of revascularization, (b) monitoring intracellular proteolysis as a possible target for therapeutic intervention, and (c) providing an impetus for standardizing the epitopes used in the troponin I assay.

Footnotes

  • Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form.

  • Employment or Leadership: V.P. Figueiredo, CAPES – Coordination for the Improvement of Higher Education Personnel.

  • Consultant or Advisory Role: None declared.

  • Stock Ownership: None declared.

  • Honoraria: None declared.

  • Research Funding: R. Schulz, Canadian Institutes of Health Research; P.M. Hwang, University Hospital Foundation.

  • Expert Testimony: V.P. Figueiredo, University of Alberta.

  • Patents: None declared.

  • Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or final approval of manuscript.

  • Received October 5, 2017.
  • Accepted January 19, 2018.
  • © 2018 American Association for Clinical Chemistry
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The Journal of Applied Laboratory Medicine: 3 (3)
Vol. 3, Issue 3
November 2018
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Proteolytic Digestion of Serum Cardiac Troponin I as Marker of Ischemic Severity
Somaya Zahran, Vivian P. Figueiredo, Michelle M. Graham, Richard Schulz, Peter M. Hwang
The Journal of Applied Laboratory Medicine Nov 2018, 3 (3) 450-455; DOI: 10.1373/jalm.2017.025254
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Proteolytic Digestion of Serum Cardiac Troponin I as Marker of Ischemic Severity
Somaya Zahran, Vivian P. Figueiredo, Michelle M. Graham, Richard Schulz, Peter M. Hwang
The Journal of Applied Laboratory Medicine Nov 2018, 3 (3) 450-455; DOI: 10.1373/jalm.2017.025254

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