Developing the next generation of cardiac markers: disease-induced modifications of troponin I.

Troponin I (TnI) and Troponin T (TnT) have evolved into arguably the two most important diagnostic markers for acute myocardial injury. Part of their diagnostic utility lies in the uniquely important roles that both TnI and TnT play in the calcium-dependent regulation of cardiac muscle contraction. Both proteins undergo extensive physiologic regulation, principally through phosphorylation, as well as specific disease-induced pathologic modifications, including phosphorylation, oxidation, and proteolysis. Many, if not all, of these protein modifications in some way modulate contractility, and when detected in serum may therefore provide important information about both the disease state and functional status of the heart. However, the complexity of the TnI (and TnT) forms in the serum is large, which leads to difficulty in detecting all of the Tn subunits in serum, and hence interpreting the biologic significance of each modified product. But, as diagnostic tools and modalities improve, our ability to monitor and detect specific disease-induced modified forms of proteins will inevitably lead to better and more specific diagnoses and therapies.