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Revision of the troponin T release mechanism from damaged human myocardium
Karin Starnberg1, Anders Jeppsson2, Bertil Lindahl3
1Department of Clinical Chemistry and Transfusion Medicine and.
Insights
Cardiac troponin T (cTnT) is more easily released from heart tissue than previously thought. This finding suggests that slow blood flow may contribute to elevated cTnT levels after heart attacks.
Area of Science:
- Biochemistry
- Cardiology
- Molecular Biology
Background:
- Cardiac troponin T (cTnT) is a biomarker released from damaged heart tissue during acute myocardial infarction.
- Previous assumptions suggested most cTnT is tightly bound and released slowly from necrotic cardiomyocytes.
- This was based on low extraction rates in cold, low-salt buffers, implying a large irreversibly bound fraction.
Purpose of the Study:
- To investigate the in vitro extraction efficiency of cTnT from human cardiac tissue under physiological conditions.
- To re-evaluate the size of the diffusible fraction of cTnT in cardiac tissue.
Main Methods:
- Extraction of cTnT from human cardiac tissue using human serum at 37 °C.
- Varied extraction volume to assess its impact on cTnT release.
- Compared cTnT extraction with that of myoglobin and creatinine kinase.
Main Results:
- Over 80% of cTnT was extracted from cardiac tissue within 90 minutes using large serum volumes at 37 °C.
- The release ratio was highly dependent on extraction volume; only 3% was released with equal serum and tissue volumes.
- Extraction of myoglobin and creatinine kinase was less sensitive to these conditions.
Conclusions:
- The diffusible fraction of cTnT in vivo is likely larger than previously estimated.
- cTnT release is not fixed but influenced by local plasma flow.
- Sustained elevated cTnT levels post-myocardial infarction may be partly due to slow washout of reversibly bound cTnT.
Background:
Cardiac troponin T (cTnT) is released from damaged heart tissue in patients with acute myocardial infarction. It is presumed that most cTnT is tightly bound and released following the degradation of myofibrils in necrotic cardiomyocytes, resulting in sustained increases in circulating cTnT. Evidence of a large irreversibly bound fraction is based on the inability to extract most cTnT from cardiac tissue in cold low-salt extraction buffers.
Methods:
Here we examined in vitro extraction of cTnT from human cardiac tissue in serum at 37 °C.
Results:
We found that over 80% of the cTnT can be extracted from human cardiac tissue in 90 min using large volumes of human serum at 37 °C. The release ratio was highly dependent on the extraction volume and was only 3% if an equal volume of serum and heart tissue was used. In contrast, extraction of the cytoplasmic cardiac damage markers myoglobin and creatinine kinase was much less affected by changing these conditions. Purified cTnT was poorly soluble in a low-salt extraction buffer at 0 °C, previously used to define the free cTnT fraction.
Conclusions:
Our data indicate that the diffusible fraction of cTnT is likely substantially larger in vivo than previously reported and likely is not fixed but dependent on local plasma flow. It is therefore possible that the sustained increase in circulating cTnT after myocardial infarction is at least in part due to a slow washout of cTnT that interacts reversibly with tropomyosin in myofibrils.