Troponin degradation products: more specific marker for myocardial infarction

Introduction Myocardial infarction (MI) is the death of cardiac muscle in the setting of severe ischemia (lack of oxygen and nutrient supply). Assay of serum troponin I (TnI) is the biochemical gold standard for detecting MI. With the development of high sensitivity assays, TnI is being detected in milder conditions such as reversible tachycardia or myocardial ischemia in the absence of radiologic evidence for infarct. Different types of MI are classified clinically: type 1 MI being the classic “heart attack” where the irreversible infarct necessitates a timely intervention. In contrast, type 2 MI is precipitated by a physiologic stressor (e.g. tachyarrhythmia, sepsis, or anemia) that causes ischemia in vulnerable regions of the heart. It is very important to differentiate irreversible infarct from reversible ischemia with a novel biomarker because the treatments are very different. Rationale While the mechanisms leading to TnI release are poorly understood, it is generally accepted that intracellular proteases are differentially activated in ischemia and in cell death. Cardiac TnI has intrinsically disordered N‐ and C‐terminal ends that are exposed and vulnerable to proteolytic digestion. TnI proteolysis products may be more rational and specific markers for irreversible cardiomyocyte death than its total level in the blood. Methods We collected blood samples from 29 hospitalised patients with elevated cTnI. We quantitated proteolytic degradation using sandwich ELISAs to specifically detect the N‐terminal, core, or C‐terminal regions of TnI using commercial antibodies (M18, MF4, and 560, respectively). Results We observed a wide variation in the degree of proteolytic degradation of TnI across the patients' samples. Interestingly, degradation of TnI at both N‐ and C‐termini in type 1 MI samples was detected. However, the C‐terminus degradation was more robust, consistent and proportional to the severity of the infarct. On the other hand, there was less degradation observed in type 2 MI samples, indicating that TnI is released in a more intact form. Conclusions Proteolytic degradation of TnI at its C‐terminus is a more specific marker for clinically significant MI than total TnI level. Making a distinction between intact and degraded forms of TnI may be useful for identifying patients with focal infarct in need of urgent revascularization and monitoring intracellular proteolysis as a possible target for therapeutic intervention. Support or Funding Information This work was funded by the University of Alberta Hospital Foundation, CIHR, startup funds from the Department of Medicine and Faculty of Medicine & Dentistry in the University of Alberta, and the Hwang Professional Corporation

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