title: 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 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.
authors.affiliation: INSERM, U744, Lille, France; Institut Pasteur de Lille, Lille, France; University of Lille 2, IFR141, Lille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dubois-Deruy
authors.forename: Aude
authors.initials: A
authors.lastname: Belliard
authors.forename: Paul
authors.initials: P
authors.lastname: Mulder
authors.forename: Maggy
authors.initials: M
authors.lastname: Chwastyniak
authors.forename: Olivia
authors.initials: O
authors.lastname: Beseme
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Henry
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Florence
authors.initials: F
authors.lastname: Pinet
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000737:chemistry*; D020107:Troponin T / Q000097:blood* / Q000737:chemistry
chemical_list: D015415:Biomarkers; D020107:Troponin T; D012694:Serine
keywords: Rat; biomarker; heart failure; ivabradine; myocardial infarction; phosphorylated troponin T; plasma
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