A Revised Perspective on the Evolution of Troponin I and Troponin T Gene Families in Vertebrates.

The troponin (Tn) complex, responsible for the Ca2+ activation of striated muscle, is composed of three interacting protein subunits: TnC, TnI, and TnT, encoded by TNNC, TNNI, and TNNT genes. TNNI and TNNT are sister gene families, and in mammals the three TNNI paralogs (TNNI1, TNNI2, TNNI3), which encode proteins with tissue-specific expression, are each in close genomic proximity with one of the three TNNT paralogs (TNNT2, TNNT3, TNNT1, respectively). It has been widely presumed that all vertebrates broadly possess genes of these same three classes, although earlier work has overlooked jawless fishes (cyclostomes) and cartilaginous fishes (chimeras, rays, and sharks), which are distantly related to other jawed vertebrates. With a new phylogenetic and synteny analysis of a diverse array of vertebrates including these taxonomic groups, we define five distinct TNNI classes (TNNI1-5), with TNNI4 and TNNI5 being only present in non-amniote vertebrates and typically found in tandem, and four classes of TNNT (TNNT1-4). These genes are located in four genomic loci that were generated by the 2R whole-genome duplications. TNNI3, encoding "cardiac TnI" in tetrapods, was independently lost in cartilaginous and ray-finned fishes. Instead, ray-finned fishes predominantly express TNNI1 in the heart. TNNI5 is highly expressed in shark hearts and contains a N-terminal extension similar to that of TNNI3 found in tetrapod hearts. Given that TNNI3 and TNNI5 are distantly related, this supports the hypothesis that the N-terminal extension may be an ancestral feature of vertebrate TNNI and not an innovation unique to TNNI3, as has been commonly believed.

Computational binding study of cardiac troponin I antibody towards cardiac versus skeletal troponin I.

A computational study of the interaction of cardiac troponin I (cTnI) with its specific antibody and of that antibody with skeletal troponin I (sTnI), the principal interferon of cTnI, is carried out. Computational and simulation tools such as FTSite, FTMap, FTDock and pyDock are used to determine the binding sites of these molecules and to study their interactions and molecular docking performance, allowing us to obtain relevant information related with the antigen-antibody interaction for each of the targets. In the context of the development of immunosensing platforms, this type of computational analysis allows performing a preliminary in-silico affinity study of the available bioreceptors for a better selection when moving to the experimental stage, with the subsequent saving in cost and time.

The ratio of N-terminal pro-B-type natriuretic peptide to troponin I for differentiating acute coronary syndrome.

INTRODUCTION: It is difficult to differentiate whether coronary or non-coronary causes in patients with elevated troponin I (TnI) in emergency department (ED). The aim of this study was to develop a clinical decision tool for differentiating a coronary cause in the patients with elevated TnI. METHODS: This was a retrospective observational study that enrolled consecutive ED patients. Patients were included in the study if they were ≥16 years of age, had admitted through ED with a medical illness, and TnI levels at initial evaluation in the ED were ≥0.2 ng/mL. Patients diagnosed with ST elevation myocardial infarction or congestive heart failure were excluded. Coronary angiography, electrocardiogram, laboratory results, echocardiography, and clinical characteristics were analyzed. RESULTS: Among the included 1441 patients, 603 and 838 patients were categorized into an acute coronary syndrome (ACS) group and non-acute coronary syndrome (non-ACS) group, respectively. The ratio of N-terminal pro-Btype natriuretic peptide (NT-proBNP) to TnI was significantly higher in the non-ACS group compared to the ACS group. The AUC of NT-proBNP/TnI (0.805, 95% CI, 0.784-0.826) was significantly superior to that of NT-proBNP/creatinine kinase-MB, TnI, and NT-proBNP. The patients of the non-ACS group with high levels of TnI and BNP showed more critically ill manifestation at the time of presentation and higher mortality. CONCLUSION: NT-proBNP/TnI may help to distinguish medical patients with elevated TnI whether the elevated TnIs were caused from ACSs or from conditions other than ACS.

Cardiac troponin I: prothrombotic risk marker in non-valvular atrial fibrillation.

BACKGROUND: Evidence of a link between small rises in cardiac troponin I (cTnI) and an increased risk of thromboembolic events (TE) in atrial fibrillation (AF) is currently scarce. OBJECTIVES: We aimed to assess the relation between cTnI and findings of an increased thromboembolic risk in patients with non-valvular AF using transesophageal echocardiography. METHODS: We have included 245 patients performing transthoracic and transesophageal echocardiogram, alongside with laboratory assessment (including cTnI) in a cross-sectional survey. Changes associated to TE were sought on transesophageal echocardiogram: left atrial or left atrial appendage thrombus, dense spontaneous echocardiographic contrast, low flow velocities in the left atrial appendage and protuberant aortic plaques. Comparisons were performed according to the baseline concentration of cTnI, regarding the prevalence of these changes. We have added cTnI to CHADS2 and CHA2DS2-VASc scores in order to assess its capability to refine risk stratification using transesophageal markers as surrogate endpoints and assessed it by means of ROC-curve analysis and Net Reclassification Improvement (NRI). RESULTS: A direct relation between rising concentrations of cTnI and a higher prevalence of transesophageal echocardiogram changes was found. Furthermore, the addition of cTnI to CHADS2 and CHA2DS2-VASc scores improved their ability to predict changes associated to TE on transesophageal echocardiography both through ROC-curve analysis and NRI. CONCLUSION: cTnI seems to be associated to thromboembolic risk in patients with AF. The possible role of cTnI in the refinement of risk stratification schemes needs to be tested in further prospective studies using clinical endpoints.

The molecular structures and expression patterns of zebrafish troponin I genes.

Troponin I (TnnI), a constituent of the troponin complex on the thin filament, providers a calcium-sensitive switch for striated muscle contraction. Cardiac TnnI is, therefore, a highly sensitive and specific marker of myocardial injury in acute coronary syndromes. The TnnI gene, which has been identified in birds and mammals , encodes the isoforms expressed in cardiac muscle fast skeletal muscle and slow skeletal muscle. However, very little is known about the TnnI gene in lower vertebrates. Here, we cloned and characterized the molecular structures and expression patterns of three types of zebrafish tnni genes: tnni1, tnni2, and tnn-HC (Heart and craniofacial). Based on the unrooted radial gene tree analysis of the TnnI gene among vertebrates, the zebrafish Tnni1 and TnnI2 we cloned were homologous of the slow muscle TnnI1 and fast muscle TnnI2 of other vertebrates, respectively. In addition, reverse transcription-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization demonstrated that zebrafish tnni1 and tnni2 transcripts were not detectable in the somites until 16 h post-fertilization (hpf), after which they were identified as slow-and fast muscle-specific, respectively . Interestingly, tnni-HC, a novel tnni isoform of zebrafish was expressed exclusive in heart during early cardiogenesis as 16 hpf, but then extended its expression in craniofacial muscle after 48 hpf. Thus, using zebrafish as our system model, it is suggested that the results, as noted above, may provide more insight into the molecular structure and expression pattens of the lower vertebrate TnnI gene.

The slow isoform of Xenopus troponin I is expressed in developing skeletal muscle but not in the heart.

In birds and mammals three isoforms of troponin I (TnI) exist; a slow (TnIs), a fast (TnIf) and a cardiac (TnIc). Although each of these isoforms is expressed in the adult forms of these organisms in a muscle fiber-type-specific manner, the gene encoding TnIs is also expressed within the developing heart of these vertebrates. Herein, our results demonstrate that the developing heart of Xenopus laevis, unlike its counterpart in birds and mammals, does not express the gene encoding the TnIs isoform and that the expression of this gene, as well as the one encoding the Xenopus TnIf isoform, is restricted to skeletal muscle.