Background-Left ventricular (LV) remodeling after acute myocardial infarction is associated with adverse prognosis.MicroRNAs (miRNAs) regulate the expression of several genes involved in LV remodeling. Our aim was to identify miRNAs associated with LV remodeling after acute myocardial infarction. Methods and Results-We studied 90 patients after first ST-segment-elevation acute myocardial infarction. A derivation cohort consisted of 60 patients characterized by echocardiography predischarge and at 6-month follow-up. Thirty patients characterized by magnetic resonance imaging predischarge and at 4-month follow-up were the validation cohort. Remodeling was defined as an increase in LV end-diastolic volume (ΔEDV>0) between discharge and follow-up. Circulating miRNAs were measured by microarrays and polymerase chain reaction. Using a systems-based approach, we identified several miRNAs potentially involved in LV remodeling. In the derivation cohort, one of these miRNAs, miR-150, was downregulated in patients with remodeling (ΔEDV>0) compared with patients without remodeling (ΔEDV≤0). In the validation cohort, patients with remodeling had 2-fold lower levels of miR-150 than those without (P=0.03). miR-150 outperformed N-terminal pro-brain natriuretic peptide to predict remodeling (area under the receiver-operating characteristic curve of 0.74 and 0.60, respectively). miR-150 reclassified 54% (95% confidence interval, 5-102; P=0.03) of patients misclassified by N-terminal pro-brain natriuretic peptide and 59% (95% confidence interval, 9-108; P=0.02) of patients misclassified by a multiparameter clinical model, including age, sex, and admission levels of troponin I, creatine kinase, and N-terminal pro-brain natriuretic peptide. hypertrophic heart 10-13 and in the circulation of patients with heart failure. Conclusions-Low14 Because miRNAs play functional roles in the development of heart failure, 15 modulation of their expression and activity has emerged as an attractive potential tool to limit the development of this condition. However, the prognostic value of miRNAs after AMI has received less attention.In a study by Widera et al, 16 circulating levels of 6 cardiacenriched miRNAs were measured in patients with acute coronary syndrome. Levels of miR-133a and miR-208b were upregulated in patients with AMI (compared with patients with unstable angina) and were associated with the risk of death. However, this association was lost after adjustment for high-sensitivity cardiac troponin T. Interestingly, circulating miRNAs follow a typical expression profile post-AMI that may be used for prognostic purposes.17 For instance, miR-208a increased 5 days post-AMI and remained elevated up to 90 days later. In a recent study evaluating the diagnostic value of circulating miRNAs in patients with AMI, we observed a weak association between cardiac-enriched miR-208b and miR-499 and LV dysfunction. 18Using a systems-based approach, combining analyses of miRNA profiles, obtained by microarrays, with networks of miRNA gene interactions, ...

Background T cell Ig and ITIM domain (TIGIT)/CD226 pathway has a critical role in regulating T cell responses and has come to the forefront in cancer as a promising immunotherapeutic target. However, its role in autoimmune diseases is just beginning to be elucidated. Dermatomyositis (DM) is an autoimmune disease, in which T cell dysregulation plays a pivotal role, and importantly, it is a common immune-related adverse event in response to treatment of cancers with immune checkpoint inhibitors, but no studies have implicated the TIGIT/CD226 axis in DM. Methods We recruited 30 treatment-naïve DM patients and 26 healthy controls. Flow cytometry analysis was used to investigate the co-expression of TIGIT and CD226 on T cells in blood samples. Magnetic bead or FACS-based cell isolation, T cell proliferation assay, and intracellular cytokine staining were performed to analyze the functions of different TIGIT/CD226 phenotypes. Recombinant proteins CD155, CD112, and anti-CD226 antibodies were used to suppress the function of TIGIT/CD226-expressing CD4 T cells. Results Four distinct subsets of T cells based on TIGIT/CD226 co-expression, TIGIT+CD226−, TIGIT+CD226+, TIGIT−CD226+, and TIGIT−CD226−, were identified and characterized in DM patients. Our data showed that the function of CD4 T cell subset varied by the TIGIT/CD226 phenotype. An elevated TIGIT+CD226+ CD4 subset with enhanced effector function was observed in patients with DM, especially the patients complicated with interstitial lung disease. This subpopulation was closely related to DM activity and decreased significantly in DM remission after treatment. Furthermore, the effector function of TIGIT+CD226+ CD4 subset could be suppressed by blocking CD226. Conclusion Our data revealed that the TIGIT and CD226 expression profiles could be used to identify functionally distinct subsets of CD4 T cells and TIGIT+CD226+ CD4 T cells is a significant subset in DM with enhanced frequency and effector function. This abnormal subset could be suppressed by blocking CD226, providing insight into the therapeutic target of the TIGIT/CD226 axis.