RepoMed (Medizinische Hochschule Hannover)
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Characterization of circular RNA circZFPM2 as therapeutic target in hypertrophic cardiomyopathy
No full textCirculating fibroblast activation protein α is reduced in acute ischemic stroke
Get PDFBackground Fibroblast activation protein α (FAP), a membrane glycoprotein with dipeptidyl-peptidase and collagenase properties, is expressed in atherosclerotic plaques and remodeling of the extracellular matrix based on fibrosis. Fibrosis is a main contributor of atrial cardiomyopathies. In acute MI, circulating FAP is associated with outcome. Here, we investigated the correlation of circulating FAP to echocardiographic parameters of atrial remodeling and neurological impairment in acute ischemic stroke. Methods Circulating FAP plasma concentrations were determined by ELISA in 47 patients with acute stroke and 22 control patients without stroke. Echocardiography was performed in all participants. Laboratory analysis, National Institutes of Health Stroke Scale (NIHSS) scoring and prolonged Holter-ECG-monitoring were performed in all stroke patients. Results Patients with acute stroke had lower circulating FAP concentrations than the control cohort (92 ± 24 vs. 106 ± 22 ng/mL, P < 0.001). There was no difference between the circulating FAP concentration comparing stroke due to atrial fibrillation, embolic stroke of undetermined source (ESUS) or atherosclerotic origin. Septal atrial conduction time (sPA-TDI) and left atrial (LA) volume index to tissue Doppler velocity (LAVI/a') representing echocardiographic parameters of LA remodeling did not correlate with FAP concentrations (sPA-TDI: r = 0.123, p = 0.31; LAVI/a': r = 0.183, p = 0.132). Stroke severity as assessed by NIHSS inversely correlated with circulating FAP (r = -0.318, p = 0.04). FAP concentration had a fair accuracy for identifying stroke in the receiver operating characteristic (ROC) analysis (AUC = 0.710, 95% CI: 0.577-0.843). A FAP concentration of 101 ng/mL discriminated between presence and absence of stroke with a sensitivity of 72% and a specificity of 77%. Lower circulating FAP concentration was associated with cardio-cerebro-vascular events within 12 months after admission. Conclusions Our study is the first to associate FAP with echocardiographic parameters of LA-remodeling and function. FAP did not correlate with sPA-TDI and LAVI/a'. However, FAP was associated with stroke, neurological impairment, and cardio-cerebral events within 12 months. Therefore, FAP might enable individualized risk stratification in ischemic stroke
Systematic pattern analyses of Vδ2+ TCRs reveal that shared "public" Vδ2+ γδ T cell clones are a consequence of rearrangement bias and a higher expansion status.
Get PDFBackground Vγ9Vδ2+ T cells are a major innate T cell subset in human peripheral blood. Their Vδ2+ VDJ-rearrangements are short and simple in the fetal thymus and gradually increase in diversity and CDR3 length along with development. So-called "public" versions of Vδ2+ TCRs are shared among individuals of all ages. However, it is unclear whether such frequently occurring "public" Vγ9Vδ2+ T cell clones are derived from the fetal thymus and whether they are fitter to proliferate and persist than infrequent "private" clones. Methods Shared "public" Vδ2+ TCRs were identified from Vδ2+ TCR-repertoires collected from 89 individuals, including newborns (cord blood), infants, and adults (peripheral blood). Distance matrices of Vδ2+ CDR3 were generated by TCRdist3 and then embedded into a UMAP for visualizing the heterogeneity of Vδ2+ TCRs. Results Vδ2+ CDR3 distance matrix embedded by UMAP revealed that the heterogeneity of Vδ2+ TCRs is primarily determined by the J-usage and CDR3aa length, while age or publicity-specific motifs were not found. The most prevalent public Vδ2+ TCRs showed germline-like rearrangement with low N-insertions. Age-related features were also identified. Public Vδ2+ TRDJ1 TCRs from cord blood showed higher N-insertions and longer CDR3 lengths. Synonymous codons resulting from VDJ rearrangement also contribute to the generation of public Vδ2+ TCRs. Each public TCR was always produced by multiple different transcripts, even with different D gene usage, and the publicity of Vδ2+ TCRs was positively associated with expansion status. Conclusion To conclude, the heterogeneity of Vδ2+ TCRs is mainly determined by TRDJ-usage and the length of CDR3aa sequences. Public Vδ2+ TCRs result from germline-like rearrangement and synonymous codons, associated with a higher expansion status
Depressivität, Angst, Progredienzangst und emotionale Erregung bei Paaren nach Kunstherzimplantation
Get PDFADAMTS-13 activity in stroke of known and unknown cause: relation to vascular risk factor burden
Get PDFBackground The identification of the underlying mechanism in ischemic stroke has important implications for secondary prevention. A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS-13) has antithrombotic properties and was repeatedly implicated in the pathophysiology of stroke. In this study, we, therefore, aimed to investigate whether ADAMTS-13 is associated with stroke etiology and the burden of vascular risk factors. Methods We determined ADAMTS-13 activity in two prospectively recruited stroke cohorts in the long-term course after the event. Cohort 1 (n = 88) consisted of patients who suffered a stroke due to embolic stroke of undetermined source (ESUS), cardioembolic stroke due to atrial fibrillation (AF), large-artery atherosclerosis, or small vessel disease. In cohort 2, patients with cryptogenic stroke and patent foramen ovale (PFO) scheduled for PFO closure (n = 38) were enrolled. As measures of vascular risk factor burden, the CHA2DS2VASC score, the Essen Stroke Risk Score (ESRS), and the Risk of Paradoxical Embolism (RoPE) score were calculated, as appropriate. Results ADAMTS-13 activity was lower in patients with AF-related stroke compared to patients with ESUS (p = 0.0227), which was, however, due to confounding by vascular risk factors. ADAMTS-13 activity inversely correlated with the ESRS (r = -0.452, p < 0.001) and CHA2DS2VASC (r = -0.375, p < 0.001) in cohort 1. In accordance with these findings, we found a positive correlation between ADAMTS-13 activity and the RoPE score in cohort 2 (r = 0.413, p = 0.010). Conclusion ADAMTS-13 activity is inversely correlated with the number of vascular risk factors across different stroke etiologies. Further study is warranted to establish ADAMTS-13 as a mediator of cerebrovascular risk
