Circulating plasma serine208-phosphorylated troponin T levels are indicator of cardiac dysfunction
Emilie Dubois-Deruy1, Aude Belliard, Paul Mulder
1INSERM, U744, Lille, France; Institut Pasteur de Lille, Lille, France; University of Lille 2, IFR141, Lille, France.
Insights
Phosphorylated troponin T (P-Ser(208)-TnT) shows promise as a novel biomarker for predicting heart failure (HF) after myocardial infarction (MI). Its levels decrease in HF and increase with successful treatment, indicating its potential for monitoring HF progression and therapeutic efficacy.
Area of Science:
- Cardiology
- Biomarker Discovery
- Proteomics
Background:
- Heart failure (HF) post-myocardial infarction (MI) involves left ventricular (LV) remodeling, which is difficult to predict clinically.
- Previous phosphoproteomic studies identified decreased serine(208)-phosphorylated troponin T (P-Ser(208)-TnT) in the LV of HF rats.
Purpose of the Study:
- To evaluate P-Ser(208)-TnT as a plasma biomarker for HF following MI.
- To compare its performance against established biomarkers like B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), C-reactive protein (CRP), and tissue inhibitor of metalloproteinase I (TIMP-1).
- To assess its capacity to reflect pharmacological improvement in HF.
Main Methods:
- Utilized x-MAP technology for multiplex biomarker analysis.
- Compared plasma biomarker levels in rats with induced MI (HF model) versus control rats.
- Assessed P-Ser(208)-TnT levels in relation to echocardiographic and hemodynamic parameters.
- Evaluated the effect of ivabradine treatment on P-Ser(208)-TnT levels and LV function.
Main Results:
- MI rats showed increased BNP, troponin T (TnT), and cTnI, but decreased P-Ser(208)-TnT and TIMP-1 compared to controls; CRP levels remained unchanged.
- Plasma P-Ser(208)-TnT levels correlated significantly with cardiac function parameters.
- Ivabradine treatment improved LV function and increased plasma P-Ser(208)-TnT levels in MI rats.
- No excess phosphatase activity was found to explain decreased P-Ser(208)-TnT in HF rats.
Conclusions:
- Circulating P-Ser(208)-TnT is a sensitive indicator of cardiac dysfunction post-MI.
- P-Ser(208)-TnT has potential as a novel biomarker for HF following MI.
- P-Ser(208)-TnT may serve as a surrogate marker for successful HF treatment efficacy.
Abstract:
Heart failure (HF) following myocardial infarction (MI) is characterized by progressive alterations of left ventricular (LV) structure and function, named LV remodelling. Although several risk factors such as infarct size have been identified, HF remains difficult to predict in clinical practice. Recently, using phosphoproteomic technology, we found that serine(208)-phosphorylated troponin T (P-Ser(208)-TnT) decreases in LV of HF rats. Our aim was to determine the performance of P-Ser(208)-TnT as plasma biomarker of HF compared to conventional cardiac biomarkers such as B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), C-reactive protein (CRP) or tissue inhibitor of metalloproteinase I (TIMP-1) measured by x-MAP technology, as well as its capacity to reflect a pharmacological improvement of HF. We observed a significant increase of BNP, TnT and cTnI levels and a significant decrease of P-Ser(208)-TnT and TIMP-1 in the plasma of 2-month-MI rats compared with control rats with no modulation of CRP level. Circulating levels of P-Ser(208)-TnT were shown to be associated with most of the echocardiographic and haemodynamic parameters of cardiac function. We verified that the decrease of P-Ser(208)-TnT was not because of an excess of phosphatase activity in plasma of HF rats. Two-month-MI rats treated with the heart rate reducing agent ivabradine had improved LV function and increased plasma levels of P-Ser(208)-TnT. Thus, circulating phosphorylated troponin T is a highly sensitive biological indicator of cardiac dysfunction and has the potentiality of a new biomarker of HF post-MI, and of a surrogate marker for the efficacy of a successful treatment of HF.
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