AIMS: Chronic heart failure following myocardial infarction (MI) is characterized by progressive left ventricular remodelling (LVR). Despite significant improvements in MI management, LVR remains a frequent complication. Although several risk factors have been identified, such as infarct size, LVR is difficult to predict in clinical practice. METHODS AND RESULTS: Using a rat model of MI and phosphoproteomic technology, we discovered that remodelling is associated with decreased levels of myocardial and plasma serine(208)-phosphorylated troponin T (TnT). To confirm the association in human plasma, we developed new specific polyclonal antibodies against human/rat serine(207/208)-phosphorylated TnT and tested plasma obtained in the first week after MI from patients with low, intermediate, and high remodelling a year later. We observed a significant decrease of serine(207)-phosphorylated TnT and of the serine(207)-phosphorylated TnT/total TnT ratio in those with intermediate or high LVR. These differences remained statistically significant when adjusted for other determinants of LVR. In contrast, baseline B-type natriuretic peptide levels were not associated with LVR. CONCLUSION: The level of circulating phosphorylated TnT could be a new biomarker of LVR.
AIMS: Chronic heart failure following myocardial infarction (MI) is characterized by progressive left ventricular remodelling (LVR). Despite significant improvements in MI management, LVR remains a frequent complication. Although several risk factors have been identified, such as infarct size, LVR is difficult to predict in clinical practice. METHODS AND RESULTS: Using a rat model of MI and phosphoproteomic technology, we discovered that remodelling is associated with decreased levels of myocardial and plasma serine(208)-phosphorylated troponin T (TnT). To confirm the association in human plasma, we developed new specific polyclonal antibodies against human/ratserine(207/208)-phosphorylated TnT and tested plasma obtained in the first week after MI from patients with low, intermediate, and high remodelling a year later. We observed a significant decrease of serine(207)-phosphorylated TnT and of the serine(207)-phosphorylated TnT/total TnT ratio in those with intermediate or high LVR. These differences remained statistically significant when adjusted for other determinants of LVR. In contrast, baseline B-type natriuretic peptide levels were not associated with LVR. CONCLUSION: The level of circulating phosphorylated TnT could be a new biomarker of LVR.
Authors: Uwe Kirchhefer; Christiane Brekle; John Eskandar; Gunnar Isensee; Dana Kučerová; Frank U Müller; Florence Pinet; Jan S Schulte; Matthias D Seidl; Peter Boknik Journal: J Biol Chem Date: 2014-10-15 Impact factor: 5.157
Authors: Sumeyye Yar; Shamim A K Chowdhury; Robert T Davis; Minae Kobayashi; Michelle M Monasky; Sudarsan Rajan; Beata M Wolska; Vadim Gaponenko; Tomoyoshi Kobayashi; David F Wieczorek; R John Solaro Journal: J Biol Chem Date: 2013-04-22 Impact factor: 5.157