Troponin T Research Articles

Air Bubbles around the Heart: A Rare Case Report of Pneumohydropericardium in Heart Transplantation

Abstract Background Pneumohydropericardium is a rare but significant condition characterized by the presence of both air and fluid in the pericardial space. It is often associated with trauma, invasive procedures, or thoracic pathologies, and its occurrence following heart transplantation is particularly unusual. Early recognition is essential to prevent complications such as cardiac tamponade, although conservative management can be effective in cases without hemodynamic compromise. Case Summary We present the case of a 40-year-old woman with a history of hypokinetic-dilative cardiomyopathy and heterozygous for TNNT2 gene mutation (c.547C>T p.Arg183Trp), who underwent orthotopic heart transplantation. Following the procedure, she developed pneumohydropericardium, identified by echocardiography as air microbubbles and fluid in the pericardial space, without associated hemodynamic instability. The condition was monitored with serial echocardiograms, and no invasive intervention was required. The air microbubbles resolved after 16 days of echocardiographic follow-up, and the patient was discharged in stable condition. At follow-up, she showed no recurrence of the pneumohydropericardium. Discussion This case highlights pneumohydropericardium as a rare post-transplant complication that, when detected early and closely monitored, can be managed conservatively without severe outcomes. While pneumohydropericardium has been previously reported in association with other conditions, its post-transplant manifestation is rare and warrants further awareness. Echocardiographic surveillance played a key role in guiding management, as invasive procedures were avoided, and the patient remained hemodynamically stable throughout. This case underscores the importance of recognizing and managing pneumohydropericardium in heart transplant patients to ensure optimal outcomes

Cardiomyocyte Foxp1‐Specific Deletion Promotes Post‐injury Heart Regeneration via Targeting Usp20‐HIF1ɑ‐Hand1 Signaling Pathway

AbstractThe adult mammalian heart has limited regenerative capacity to replace lost tissue after a major injury. Forkhead box P1 (Foxp1) regulates embryonic cardiomyocyte proliferation and heart development. However, whether Foxp1 participates in postnatal‐injury cardiomyocyte proliferation and heart regeneration remains unclear. This study demonstrates that Foxp1 is downregulated at border zone cardiomyocytes of both neonatal apical resection and adult myocardial infarction. Analysis of the Single‐cell transcriptome database reveals reduced Foxp1 expression in the cardiomyocyte population with high regenerative capacity. Cardiomyocyte‐Foxp1 loss‐of‐function significantly promotes, whereas cardiomyocytes‐Foxp1 gain‐of‐function suppresses cardiomyocyte proliferation. Mechanistically, Foxp1 directly regulates ubiquitin specific peptidase 20 (USP20), a de‐ubiquitinase that prevents hypoxia inducible factor 1ɑ (HIF1α) degradation. Thus, Foxp1 regulates HIF1α and downstream heart and neural crest derivatives expressed 1 (Hand1) to control the cardiomyocyte proliferation via metabolic transition from fatty acid oxidation to glycolysis. Finally, cardiac type troponin T2 (cTnT)‐promoter‐driven adeno‐associated virus 9 (AAV9) for Hand1 induction in cardiomyocytes significantly promoted cardiac regeneration and functional recovery. These findings may provide novel molecular strategies to promote heart regeneration and therapeutic interventions for heart failure.

Clinical Laboratory Validation Study of a High Sensitivity Troponin I Assay on a POCT (Point of Care Testing) Device.

In Acute Coronary Syndrome without ST-segment elevation, the use of high-sensitivity troponins in rapid protocols is considered the gold standard for diagnostic exclusion/confirmation, in conjunction with clinical stratification. The biggest concern regarding the techniques for troponin evaluation is the time required between collection and delivery of the result. The objective of the present study is the clinical/laboratory validation of a POCT device for TnI. In the first phase of the study, samples from 108 patients with known troponin values High Sensitivity Automated Troponin T (TnT) assay from Roche Diagnostics were analyzed for analytical comparability between hs-cTnI of the Analyzer Atellica® vTLi and hs-cTnT Cobas®. The second phase of the study was performed with samples from 51 patients who reported to the emergency department with chest pain for a clinical prospective evaluation and correlation between the hs-cTnI assays of the Analyzer Atellica® vTLi, hs-cTnT Cobas® and Atellica IM 1300. There was a correlation between the POCT Atellica® vTLi and hs-cTnT Cobas® in the serum samples of the control group (r = 0.660, p < 0.0001). Besides, there was a correlation between the Atellica® vTLi, serum hs-cTnT Cobas®, plasma hs-cTnT Cobas®, serum Atellica IM and plasma Atellica IM 1300 platforms in the second phase (p < 0.0001 in all cases). In the present study, the Siemens POCT Atellica® vTLi device showed excellent performance in laboratory validation and correlation with the high-sensitivity TnT assay in different troponin concentration ranges. Given these results, the device can be used in institutions that intend to use a POCT device for 0- and 1-hour chest pain protocols.

Study of plasma essential element concentrations to explore markers of acute myocardial infarction.

Essential element concentrations in biological samples may be related to the pathogenesis of various diseases. Previous studies have reported that serum iron (Fe), zinc (Zn), and copper (Cu) were related to acute myocardial infarction (AMI). However, the differences in element concentrations between AMI and other cardiac disease has not been investigated. In this study, differences in plasma Fe, magnesium (Mg), Zn, Cu, calcium (Ca), inorganic phosphorus (P), and cardiac troponin T (TnT) levels in heart disease patients (AMI, angina, heart failure, and chest pain) were investigated to explore potential markers of AMI. Fe, Mg, Zn, and Cu concentrations were assayed by using a Metallo Assay kit; Ca and inorganic P were determined by using an automatic biochemical analyzer; and cardiac TnT levels were assayed by using enzyme-linked immunosorbent assay. Plasma TnT levels were higher in AMI than in other heart diseases and were negatively correlated with Cu and Ca. Fe, Cu, and inorganic P levels were within the normal range, while Mg and Ca levels were lower, and Zn levels were higher than the normal range in heart disease patients. Except Mg, no significant differences in element levels were observed among heart diseases: Mg levels were significantly higher in AMI than in heart failure. These results suggest that lower Cu and Ca levels and a higher Mg level compared with other heart diseases may be a marker of AMI.

Abstract 4134619: A Novel Missense Mutation in TNNT2 Gene in a Lebanese Pedigree With Ebstein Anomaly And Wolf-Parkinson-White Syndrome: A Case Report

Background: Ebstein anomaly (EA) is a rare congenital heart defect occurring in 1.2 to 5 in 100,000 live births, characterized by a downward displacement of the tricuspid valve, thin-walled right ventricle, and tricuspid valve regurgitation. It can present variably from asymptomatic cases to severe symptoms like arrhythmias and right-sided heart failure. EA is often associated with other anomalies such as interatrial communication and mitral valve prolapse. The condition can lead to accessory atrioventricular pathways, frequently resulting in Wolff-Parkinson-White syndrome (WPW), which involves abnormal heart electrical activity and increases the risk of sudden cardiac death. While the genetic basis of EA is not fully understood, it appears to involve multiple genes like FLNA and NKX2-5, MYH6, MYH7 suggesting a complex polygenic inheritance pattern. TNNT2 is known to be associated with Cardiomyopathy but has not been previously associated with EA and WPW. Case: In this report, we present findings from a lebanese family with EA, comprising 2 affected individuals. Whole exome sequencing in the affected individuals identified a pathogenic variant in the TNNT2 gene at coding strain position 260 (a missense mutation: C to T), resulting in the substitution of Proline with Leucine at position 87 in affected individuals (Figure 1). No variants were detected in any other candidate gene examined. Individuals I:1 and II:2 were found to be normal, with no EA findings on echocardiography. Methods: Whole exome sequencing in the patients involved collecting blood samples after obtaining consent. These samples were sent to Centogene lab, where genomic DNA is enzymatically fragmented. The regions of interest are then enriched using DNA capture probes, facilitating detailed genetic analysis. Results: The whole exome sequencing identified a heterozygous missense mutation in both the father and his daughter. This nonsynonymous variant is located on chromosome 1 (GRCh37) in the TNNT2 gene region. The specific variant, NM_001276345.1:c.260C&gt;T p.(Pro87Leu), was found in both individuals. Conclusion: In conclusion, the genetic basis of EA is rather complex and remains poorly understood. It is established that mutations in the TNNT2 gene are linked to several cardiomyopathies, none of them overlap with the described phenotype of our patients. In this report, we therefore confirm the potential role of TNNT2 gene mutation in the genetic basis of familial EA with WPW.

Abstract 4145884: Left ventricular 3D-sphericity is associated with 92 genetic loci

Introduction: Left ventricular (LV) sphericity is a measure of the degree to which the LV blood pool resembles a sphere. Analyses of cardiovascular magnetic resonance imaging (MRI) in the MESA cohort have shown that LV sphericity is an important mode of variation in cardiac structure that is associated with ischemia, heart failure, and atrial fibrillation. A recent genome-wide association study (GWAS) of a two-dimensional estimate of sphericity in 38,000 UK Biobank participants identified 4 genetic loci (near PDZRN3, HLA, PLN, and ANGPT1). Genetic contributions to three-dimensional (3D) sphericity remain unknown. Aims: To measure 3D sphericity from cardiovascular MRI at scale and characterize the genetic contributions to 3D sphericity. Methods: Deep learning models were constructed to perform semantic segmentation in the short- and long-axis view from cardiovascular MRI in UK Biobank. These models were applied to all participants with MRI. Poisson surface reconstruction was used to build 3D meshes of the left ventricle. Sphericity was estimated at end-systole and end-diastole as the area of a perfect sphere with the same volume as the left ventricle, divided by the estimated surface area from the mesh. Heritability was estimated with ldsc; GWAS was conducted with REGENIE. Results: Sphericity was estimated in 68,978 individuals, of whom 3,096 were excluded due to atrial fibrillation or atrial dysfunction, and 2,686 were excluded during genetic quality control; 63,196 participants were included in the GWAS. Ldsc heritability was 29.7% for sphericity in diastole and 26.0% for sphericity in systole. 49 genetic loci were associated with 3D sphericity in diastole as were 64 in systole (92 distinct loci). 46 of these loci were unique to sphericity and not found for other LV traits, including loci near the genes encoding calsequestrin 2, troponin T2, palladin, supervillin, and angiopoietins 1 and 2. Shared loci included those near RXFP4, encoding a relaxin-family peptide receptor, and MICU2 (previously implicated in cardiac relaxation). Conclusion: Left ventricular sphericity is heritable, with genetic underpinnings distinct from standard LV measurements.

Abstract 4137965: D-dimer as a 5-year predictor of death in females admitted with chestpain of suspected coronary origin surpasses that of males.

Background: D-dimer (DD) and fibrin monomer (FM) are endstage markers of activated coagulation and reflect prothrombotic states, and α2-antiplasmin (SERPINF2 -SF2) is the main inhibitor of fibrinolysis at the level of plasmin. Women may experience a higher rate of morbidity and mortality compared to men following a myocardial infarction (MI). We present the prognostic potential of DD, FM and SF2 in females as compared to males during 5 years follow-up in a population admitted with chest pain of suspected coronary origin. Methods: A total of 871 consecutive patients with a median age of 72.6 years (females 77.3, males 69.1) were admitted in the study. Of these, 386 were diagnosed with an acute MI based on Troponin-T (TnT) levels &gt;50 ng/L. Stepwise Cox regression models, applying normalized continuous log e /SD values, were fitted for the biomarkers with total mortality within 5 years as the dependent variable. Results: Death was recorded in 246 patients; 34.4% females vs. 27.2% males (Chi-squared test p-value = 0.02). Blood samples were available for analysis of DD, FM and SF2 in 820, 810 and 846 patients, respectively. Females had a signficantly higher mean of DD (p&lt;0.0001) and FM (p=0.0020) than males and SF2 did not differ (p=0.0825). In the univariate analysis, a highly significant association between DD and total death was observed in both sexes (p&lt;0.001). However, after adjusting for confounders in the multivariable analysis, the associations remained significant in females but not in males, with an HR of 1.62 (95%CI 1.36 – 1.93), p&lt;0.0001 vs. 1.16 (95%CI 0.98 - 1.39, p=0.094, respectively, (p for interaction &lt;0.001). Similar findings were noted in the multivariable analysis of FM with HR 1.46 (95%CI 1.19 – 1.80), p=0.0003 in females vs. 1.12 (95%CI 0.93 -1.35), p=0.22 in males (p for interaction 0.056). In the univariate analysis, SF2 was not associated with all-cause mortality; p=0.56 in females vs. p=0.83 in males, and remained essentially unchanged after adjustment; p=0.84 vs. HR 0.92 (95%CI 0.78 – 1.09). p=0.35 in males, yielding a p=0.36 for interaction. Conclusion: Activated endstage coagulation was associated with total death at 5 years FU in females admitted with chest pain of suspected coronary origin, whereas plasmin inhibition was not. A significant p-value for interaction between the two sexes indicates that the prognostic value of DD surpasses that of men.

Troponin T as a risk marker for recurrent cardiovascular events in the post-discharge setting one month after acute coronary syndrome: a TRACER substudy

Abstract Background Troponin T (TnT) is a protein found in cardiac myocytes that is released during myocardial injury, such as myocardial infarction (MI). TnT levels rapidly rise during an MI, remain elevated for several days, and are a key criterion for diagnosing MI. Additionally, circulating TnT levels may offer prognostic information later, particularly during the rehabilitation phase after an acute coronary syndrome (ACS). Purpose To examine the relationship between circulating TnT at one month after hospitalisation for ACS and subsequent cardiovascular (CV) events. Methods The TRACER trial randomly assigned 12,944 patients diagnosed with non-ST-segment elevation ACS (NSTE-ACS) to receive either vorapaxar or placebo. Plasma samples were obtained after one month, and high-sensitivity (hs)-TnT was measured among 5,313 patients using the Elecsys electrochemiluminescence immunoassays. In this sub-study, the primary composite endpoint was the one-year risk of CV mortality, MI, or ischaemic stroke. Associations with outcomes were evaluated using Cox regression models, both unadjusted and adjusted for clinical baseline characteristics. Results The median concentration of hs-TnT was 11 ng/L one month after hospitalisation for ACS. Higher levels of hs-TnT at one month were associated with older age, coronary artery bypass surgery during the index ACS, male sex, a history of heart failure, renal disease, and diabetes mellitus. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 381 patients (incidence rate 5.4 per 100 person-years). Hs-TnT at one month after ACS was independently associated with the risk of the composite CV endpoint (relative hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 2.40 [1.80 – 3.20]) (see Figure 2). Similarly, hs-TnT, when added to a model including established risk factors, increased the concordance index of the multivariable model from 0.711 to 0.740 (p&amp;lt;0.001). The results were consistent across the different components of the composite endpoint. Conclusions The level of hs-TnT provides useful information on the risk of future CV events in patients when measured one month after an ACS. This information might be useful for optimising secondary preventive treatment following an ACS.Figure.Hs-TnT and composite CV outcome

Combined activation of complement and coagulation is associated with myocardial injury in ST-elevation myocardial infarction

Abstract Introduction Experimental data indicates that the complement system and the coagulation cascade can activate each other. The magnitude of this interaction in acute myocardial infarction is not known. We aimed to investigate a possible association between complement activation and coagulation activation in patients with acute ST-elevation myocardial infarction (STEMI), as well as how they relate to myocardial injury estimated by troponin T (TnT) and myocardial function assessed by echocardiography. Purpose To increase the understanding of the interaction between complement activation and coagulation activation in STEMI, and the clinical relevance to myocardial injury. Methods Blood samples were drawn after percutaneous coronary intervention (PCI) in 864 patients with STEMI. Myocardial function was measured as left ventricular ejection fraction (LVEF), estimated by visual approximation or Simpson biplane method within 3 months. Complement activation was assessed by ELISA of circulating levels of the terminal complement complex (TCC). Activation of coagulation was assessed by ELISA of prothrombin fragment 1+2 (F1+2) and D-dimer, and endogenous thrombin potential (ETP), analyzed by calibrated automated thrombogram assay. Results TCC was weakly correlated to F1+2 (r=0.086, p=0.012), D-dimer (r=0.176, p&amp;lt;0.001) and ETP (r=0.144, p&amp;lt;0.001). In univariate linear regression analysis, this association persisted for D-dimer and ETP. When adjusting for associated covariables, the association only persisted for ETP (Table 1). Patients with above-median TCC and D-dimer had significantly higher peak TnT (Figure 1). In logistic regression, having combined above-median TCC and D-dimer was predictive of an LVEF ≤40% (Table 2). Conclusion In this large STEMI cohort, complement activation by TCC was weakly associated with coagulation activation. Combined high levels of TCC and D-dimer were linked to higher peak TnT and lower LVEF, possibly reflecting greater myocardial injury. The interaction between complement and coagulation activation might be relevant for clinical outcomes in STEMI patients and warrants further investigation.

Effect of tocilizumab on endothelial and platelet-derived CXC-chemokines and their association with inflammation and myocardial injury in STEMI patients undergoing primary PCI

BackgroundTocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI) patients when administered before percutaneous coronary intervention (PCI). The mechanisms underlying ischemia-reperfusion injury remain unclear. In this sub-study, we investigated whether endothelial and platelet-derived CXC chemokines are involved, as they represent inflammatory mediators from two cell types relevant to myocardial infarction. Associations between these chemokines and neutrophils, C-reactive protein (CRP), troponin T (TnT), myocardial salvage index (MSI), microvascular obstruction (MVO), and infarct size. MethodsThis is a sub-study of the ASSAIL-MI trial, a double-blind clinical trial that randomized 199 STEMI patients to receive either 280 mg tocilizumab (n = 101) or placebo (n = 98) intravenously before PCI. Blood samples were collected prior to infusion, at day 1–2, 3–7, and at 3 and 6 months. Heparin was administered before baseline in 150 patients, while 49 received it after. We measured CXC-chemokines CXCL4, CXCL5, CXCL6, CXCL7, and CXCL12 using immunoassays. Cardiac MRI was performed in the first week and at 6 months. ResultsTocilizumab did not significantly affect CXC-chemokines levels. Although some correlations were observed between chemokine levels and neutrophil counts and CRP, none of the CXC chemokines were associated with infarct size, MSI, MVO, or TnT levels. Notably, CXCL 12 levels increased in patients who received heparin before baseline, while other CXC-chemokines decreased significantly. ConclusionThis study suggests that the beneficial effects of tocilizumab in STEMI patients are not due to changes in circulating endothelial or platelet-derived CXC-chemokines, compared to placebo. However, heparin significantly influences the levels of these chemokines.

Searching for genetic determinants for left ventricular non-compaction.

Left ventricular non-compaction (LVNC) is still a pathology around which there are numerous controversies regarding the criteria for its diagnosis, presentation, prognosis, and even classification into the appropriate group of diseases. So far, about 190 genes in which mutations may be associated with LVNC have been described, and in each of them, several to several dozen different loci have been discovered. We decided to analyze the frequency of single nucleotide variants (SNVs) in correlation to Petersen's criteria. We retrospectively analyzed the results of cardiac magnetic resonance (CMR) studies. Twenty-three patients who met Petersen's criteria agreed to participate in the research and take blood samples for genetic testing. Next, we prospectively included 24 volunteers who did not meet Petersen's criteria. Petersen's criteria were complied with ratio of non-compacted to compacted myocardium (NC/C) ≥2.3. A total of 47 DNA samples were analyzed based on the selected regions of the following genes: β-myosin heavy chain (MYH7), α-cardiac actin (ACTC1), cardiac troponin T (TNNT2), myosin binding protein-C (MYBPC3), LIM-domain binding protein 3 (LBD3), and taffazin (TAZ). In total, 248 substitutions in exons and introns were obtained for all analyzed samples. No statistically significant differences were detected between the mentioned groups. No significant difference in either downward or upward trends in the number of substitutions in relation to the increasing trabeculation is observed. We indicated differences in the occurrence of the studied SNVs between groups, especially for rs8037241 (3'UTR region of ACTC1) and rs2675686 (LDB3), but they also did not show statistical significance. Although we did not find a significant correlation between the co-occurrence of individual mutations with LVNC, it is worth noting that the presence of one of the four mutations in the range rs8037241 (ACTC1 3'UTR), rs3729998 (TNNT2e. 12), and rs727503240 (MYH7e. 39) increases the risk of LVNC more than 4 times. An inverse association between the number of SNVs and the meeting the Petersen's criteria was demonstrated for studied LDB3 region and rs397516254 in exon 39 of the MYH7 gene. To our knowledge, no studies have been published comparing the prevalence of selected SNVs in a group of healthy subjects and in a group meeting the Petersen criteria for LVNC. Among both completely healthy individuals who did not meet the Petersen criteria for LVNC as well as those with symptoms who met these criteria we found a similar incidence of SNVs in the ACTC1, TNNT2, LDB3 and MYH7 genes segments analyzed. Further studies are required to confirm or exclude "potentially protective" SNV in the 39th exon of MYH7 (rs397516254) and the role of co-occurrence of individual SNVs in rs8037241 (ACTC1 3'UTR), rs3729998 (TNNT2), and rs727503240 (MYH7) for the increase of the risk of LVNC.

Value of troponin and NT-proBNP to screen for cardiac amyloidosis after carpal tunnel syndrome surgery

BackgroundEarly diagnosis of cardiac amyloidosis (CA) is crucial due to the promising effect of disease-modifying treatment. This calls for screening strategies to identify CA patients with so-called “red flags”, such as carpal tunnel syndrome (CTS). ObjectivesThis study aims to assess Troponin-T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) as predictors for CA in patients with a history of surgery for bilateral carpal tunnel syndrome, a population suitable for systematic screening. MethodsSubjects with a history of surgery for bilateral CTS 5–15 years prior, identified using national registries were investigated for CA as per international recommendations. Sensitivity, specificity, positive and negative predictive values were assessed, and receiver operating curves were generated using logistic regression. ResultsAmong the 250 participants, 12 were diagnosed with CA, all with wild-type transthyretin amyloidosis. Elevated TnT levels (≥13 ng/L) were found in all CA patients and 25.6% (±2.8) of non-CA patients. The negative predictive value (NPV) of TnT <13 ng/L was 100%. For NT-ProBNP the NPV was 99.1% when age dependent cutoff levels were used. A combination of both biomarkers yielded an NPV of 99.1% and sensitivity of 99.7%. Early disease (Mayo or NAC stage 1) was found in 83% of identified patients with CA. ConclusionThis study demonstrates the utility of TnT and NT-ProBNP as negative predictors to exclude CA in a screening population with a history of surgery for CTS.

FUS-Mediated Inhibition of Myogenesis Elicited by Suppressing TNNT1 Production.

Myogenesis is a highly orchestrated process whereby muscle precursor cells, myoblasts, develop into muscle fibers to form skeletal muscle during embryogenesis and regenerate adult muscle. Here, we studied the RNA-binding protein FUS (fused in sarcoma), which has been implicated in muscular and neuromuscular pathologies but is poorly characterized in myogenesis. Given that FUS levels declined in human and mouse models of skeletal myogenesis, and that silencing FUS enhanced myogenesis, we hypothesized that FUS might be a repressor of myogenic differentiation. Interestingly, overexpression of FUS delayed myogenesis, accompanied by slower production of muscle differentiation markers. To identify the mechanisms through which FUS inhibits myogenesis, we uncovered RNA targets of FUS by ribonucleoprotein immunoprecipitation (RIP) followed by RNA-sequencing (RNA-seq) analysis. Stringent selection of the bound transcripts uncovered Tnnt1 mRNA, encoding troponin T1 (TNNT1), as a major effector of FUS influence on myogenesis. We found that in myoblasts, FUSretained Tnnt1 mRNA in the nucleus, preventing TNNT1 expression; however, reduction of FUS during myogenesis or by silencing FUS released Tnnt1 mRNA for export to the cytoplasm, enabling TNNT1 translation and promoting myogenesis. We propose that FUS inhibits myogenesis by suppressing TNNT1 expression through a mechanism of nuclear Tnnt1 mRNA retention.

A Common 5bp (CTTCT) Deletion Polymorphism in TNNT2 is Significantly Associated with Hypertrophic Cardiomyopathy

Troponin T is a component of the Troponin complex, which plays a major role in the regulation of myocardial contraction in response to changes in the intracellular Ca2+ion concentration. Deletion of 5bp (CTTCT) in the polypyrimidine tract of intron 3 of the cardiac Troponin T gene (TNNT2) results in cTnT2 and cTnT4 isoforms by skipping of exon 4, which was reported to be associated with hypertrophic cardiomyopathy (HCM). In the present study, we screened a common 5bp deletion polymorphism in TNNT2 gene using direct sequencing in 178 cardiomyopathy patients with significant LV hypertrophy from North India against 197 ethnically matched and clinically well-characterized healthy controls. Our study revealed a high frequency of del/del genotype in patients with HCM vs controls (p=0.000007). The deletion and insertion allele frequencies in patients and controls were (75% &amp; 25%) and (56% &amp; 44%), respectively. Further, analysis of 2056 caste and tribe groups belonging to highly diverse endogamous people inhabited in different states of India have revealed higher deletion allele frequency in both South and North Indian states compare to control group whereas the North-eastern states showed a slightly higher frequency of insertion allele. In conclusion, the deletion allele frequency in the HCM patient group is found to be significantly higher than the control group (p=&lt;.0001). Therefore, the deletion allele frequency is not only associated with LV hypertrophy in Japanese, French, and South Indian HCM patients but also in North Indian HCM patients.

Association of serum resolvin D1 with the risk of major adverse cardiovascular events in hemodialysis patients.

Resolvin D1 (RvD1) inhibits inflammation, reduces oxidative stress, and forecasts the risk of cardiovascular events, but relevant evidence in hemodialysis patients is lacking. This study intended to investigate the predictive value of RvD1 for major adverse cardiovascular events (MACE) risk in hemodialysis patients. Totally, 252 patients who underwent hemodialysis were included. Serum RvD1 was measured by enzyme-linked immunosorbent assay. Patients were followed up with a median of 12.1months. MACE was recorded during the follow-up period. RvD1 was inversely correlated with diabetes history (P = 0.002), cardiac troponin T (TnT) (P = 0.029), and high sensitivity C-reactive protein (hsCRP) (P < 0.001) in hemodialysis patients. 25 hemodialysis patients experienced MACE. RvD1 was reduced in hemodialysis patients with MACE versus those without MACE (P = 0.004). RvD1 exhibited a certain value in forecasting MACE risk, with an area under curve (AUC) of 0.675 [95% confidence interval CI: 0.565-0.786]. Increased RvD1 cut by median (P = 0.043) and cut by quartile (P = 0.042) were related to decreased accumulating MACE in hemodialysis patients. Moreover, RvD1 independently predicted declined MACE risk [odds ratio (OR) = 0.644, P = 0.045], but age (OR = 1.048, P = 0.039) and TnT (OR = 1.006, P = 0.005) independently predicted ascended MACE risk in hemodialysis patients. The combination of these independent factors displayed a good value for estimating MACE risk in hemodialysis patients with an AUC of 0.744 (95% CI: 0.640-0.849). Serum RvD1 is inversely correlated with diabetes history, TnT, and hsCRP in hemodialysis patients. More importantly, it could serve as a potential marker to predict MACE risk in these patients.

TNNT1 accelerates migration, invasion and EMT progression in lung cancer cells.

Clinically, most patients with lung cancer (LC) die from tumor spread and metastasis. Specific metastasis-related molecules can provide reference for clinical prediction of efficacy, evaluation of prognosis, and search for the best treatment plan. Troponin T1 (TNNT1) is highly expressed in various cancer tissues, which affects malignant behavior of tumor cells and is related to patients' survival and prognosis. However, the role and molecular mechanism of TNNT1 in LC invasion and metastasis have not yet been investigated. Gene expression profiling interactive analysis (GEPIA) online analysis was used to analyze TNNT1 expression in LC tissues. Quantitative real-time-polymerase chain reaction (qRT-PCR) or western blot were performed to measure TNNT1 or epithelial-to-mesenchymal transition (EMT)-related and Wnt/β-catenin pathway-related protein expression in LC cells. After TNNT1 knockdown, cell scratch healing and transwell assays were introduced to assess cell migration and invasion, respectively. TNNT1 expression in LC tissues and cells was increased. TNNT1 knockdown notably impaired LC cell migration, invasion and EMT. TNNT1 knockdown inhibited Wnt/β-catenin pathway of LC cells. Lithium chloride (LiCl) addition partially restored the inhibition of TNNT1 knockdown on migration, invasion, EMT and Wnt/β-catenin of LC cells. TNNT1 knockdown attenuated LC migration, invasion and EMT, possibly through Wnt/β-catenin signaling.

Generation of cardiomyocytes from stem cells cultured on nanofibrous scaffold: Experimental approach for attenuation of myocardial infarction

The current study was constructed to fabricate polyamide based nanofibrous scaffolds (NS) and to define the most promising one for the generation of cardiomyocytes from adipose tissue derived mesenchymal stem cells (ADMSCs). This purpose was extended to assess the potentiality of the generated cardiomyocytes in relieving myocardial infarction (MI) in rats. Production and characterization of NSs were carried out. ADMSCs were cultured on NS and induced to differentiate into cardiomyocytes by specific growth factors. Molecular analysis for myocyte-specific enhancer factor 2 C (MEF2C) and alpha sarcomeric actin (α-SCA) expression was done to confirm the differentiation of ADMSCs into cardiomyocytes for further transplantation into MI induced rats. Implantation of cells in MI afflicted rats boosted heart rate, ST height and PR interval and lessened P duration, RR, QTc and QRS intervals. Also, this type of medication minified serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzymes activity as well as serum and cardiac troponin T (Tn-T) levels and upraised serum and cardiac α-SCA and cardiac connexin 43 (CX 43) levels. Microscopic feature of cardiac tissue sections of rats in the treated groups revealed great renovation in the cardiac microarchitecture. Conclusively, this attempt gains insight into a realistic strategy for recovery of MI through systemic employment of in vitro generated cardiomyocytes.

Trigonelline, a Fenugreek Bioactive compound protects Heart tissue against alcohol intoxication: An in-vivo study focusing on antioxidant perspective

BackgroundTrigonella foenum-graecum, commonly known as fenugreek and it is used as a spice. It has antioxidant, anti-diabetic, antilipedemic and other pharmocological properties. ObjectivesThe aim of the study was to detect the cardio protective activity of Trigonelline (TG) a bioactive compound of Trigonella foenum-graecum (TF) in alcohol intoxicated rats. Material and methodsThe young wistar strain albino rats are divided in to 5 groups and treatment was given as per the experimental protocol. Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), glutathione (GSH), malondialdehyde (MDA) levels are estimated in cardiac tissue of all experimental groups. Cardiac markers creatine kinase-MB (CK-MB), troponin-T (TT), troponin-I (TI), myoglobin (MG) and serum markers alanine transaminase (AAT), aspartate transaminase (AST) and alkaline phosphatase (ALP) are estimated. Free radical scavenging activities like 2,2-diphenylpicrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and hydroxyl radical are estimated in ethanolic extract of Trigonella foenum-graecum. ResultsSOD, CAT, GPx, GR, GSH activities are depleted and MDA, CK-MB, TT, TI, MG and AAT, AST, ALP activities are elevated in alcohol intoxicated rats. Trigonelline supplementation to alcoholic rats for 30 days elevated antioxidant enzymes, depleted MDA, cardiac markers and serum markers in alcohol intoxicated rats. Free radical scavenging assay also reported that Trigonella foenum-graecum possess free radical scavenging activity. Furthermore, our histopathological evidence also proved that TG protected the cardiac tissue from alcohol induced toxicity in all the experimental rats. ConclusionOur study concluded that TG may be useful to the alcoholic and myocardial infarction subjects.

Reconstitution of peripheral blood T cell receptor β immune repertoire in immune checkpoint inhibitors associated myocarditis

PurposeImmune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis.MethodsA total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood.ResultsIn the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments.ConclusionThe reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.

Establishment of a human induced pluripotent stem cell line from a patient with dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is one of the main causes of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation worldwide. Mutations in dozens of cardiac genes have been connected to the development of DCM including the Troponin T2 gene (TNNT2). Here, we generated a human induced pluripotent stem cells (hiPSCs) from a DCM patient with a familial history that carries a missense mutation in TNNT2. The hiPSCs show typical morphology of pluripotent stem cells, expression of pluripotency markers, normal karyotype, and in vitro capacity to differentiate into all three germ layers.