Circulating plasma serine²⁰⁸‐phosphorylated troponin T levels are indicator of cardiac dysfunction

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 serine208-phosphorylated troponin T (P-Ser208-TnT) decreases in LV of HF rats. Our aim was to determine the performance of P-Ser208-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-Ser208-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-Ser208-TnT were shown to be associated with most of the echocardiographic and haemodynamic parameters of cardiac function. We verified that the decrease of P-Ser208-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-Ser208-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.

Increased level of phosphorylated desmin and its degradation products in heart failure

“…Novel determinants of post-myocardial infarction (MI)-HF were already revealed by previous proteomic [3] and phosphoproteomic [4] approaches. We recently discovered that HF is associated with decreased levels of myocardial and plasma serine 208 -phosphorylated troponin T (TnT) in an experimental rat model of HF and confirmed the same decrease in plasma of patients with high LV remodeling post-MI, suggesting that the level of circulating phosphorylated TnT could be new biomarker of LV remodeling and may help to predict the development of HF after MI [5] . More recently, seven proteins were found differentially expressed in cardiac tissues in a mouse model of HF (calcineurin transgenic mice) and their presence in plasma of HF mouse models but also in HF patients have been investigated [6] .…”

Interplay Between Phosphorylation and O-GlcNAcylation of Sarcomeric Proteins in Ischemic Heart Failure

“…We previously investigated cardiac phosphoproteomic changes associated with LV remodeling and dysfunction in this HF-rat model. At 2 months after surgery, proteomic analysis revealed different LV phosphoproteomic patterns between the sham- and HF-rats ( 16 ). We previously identified two spots as being desmin ( 11 ).…”

In‐depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis

“…So far, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) is established as useful non‐invasive indicator of cardiac remodelling and dysfunction 7‐9 . Elevated cardiac troponins are demonstrated as markers of increased risk for progressive left ventricular (LV) dysfunction in chronic heart failure 10,11 . Soluble suppression of tumorigenicity 2 is a predictor of reverse left ventricular remodelling 12,13 .…”