FADD, Caspase-3, and Caspase-8 and Incidence of Coronary Events

Xue, Ling; Borné, Yan; Mattisson, Ingrid Yao; Wigren, Maria; Melander, Olle; Ohro-Melander, Marju; Bengtsson, Eva; Fredrikson, Gunilla Nordin; Nilsson, Jan; Engström, Gunnar

doi:10.1161/atvbaha.117.308995

“…It is involved in beta-cell apoptosis in diabetes (23), but also in the activation of T, B, and natural killer cells and macrophage differentiation. It is not well understood which processes lead to the release of this protein into the circulation, but it is noteworthy that higher circulating CASP-8 levels were associated with a higher risk of type 2 diabetes and coronary events (24,25). SIDD represents the opposite extreme compared to SIRD with the most pronounced insulin deficiency and the lowest circulating levels of biomarkers of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Differences in Biomarkers of Inflammation Between Novel Subgroups of Recent-Onset Diabetes

Herder

¹

,

Maalmi

²

,

Straßburger

³

et al. 2021

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A novel clustering approach identified five subgroups of diabetes with distinct progression trajectories of complications. We hypothesized that these subgroups differ in multiple biomarkers of inflammation. Serum levels of 74 biomarkers of inflammation were measured in 414 individuals with recent adult-onset diabetes from the German Diabetes Study (GDS) allocated to five subgroups based on data-driven analysis. Pairwise differences between subgroups for biomarkers were assessed with generalized linear mixed models before (model 1) and after adjustment (model 2) for the clustering variables. Participants were assigned to five subgroups: severe autoimmune diabetes (SAID, 21%), severe insulin-deficient diabetes (SIDD, 3%), severe insulin-resistant diabetes (SIRD, 9%), mild obesity-related diabetes (MOD, 32%) and mild age-related diabetes (MARD, 35%). In model 1, 23 biomarkers showed ≥1 pairwise difference between subgroups (Bonferroni-corrected p<0.0007). Biomarker levels were generally highest in SIRD and lowest in SIDD. All 23 biomarkers correlated with ≥1 of the clustering variables. In model 2, three biomarkers (CASP-8, EN-RAGE, IL-6) showed at least one pairwise difference between subgroups (e.g. lower CASP8, EN-RAGE and IL-6 in SIDD vs. all other subgroups, all p<0.0007). Thus, novel diabetes subgroups show multiple differences in biomarkers of inflammation, underlining a prominent role of inflammatory pathways in particular in SIRD.

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“…CASP8 polymorphic variants (-652 6N del/ins, IVS12-19G>A) could predict the risk of CAD [34]. Furthermore, high CASP8 levels have an association with elevated incidence of coronary diseases [35]. GzmB expression is increased in blood and tissues of CAD patients compared to healthy individuals [34].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Dysregulated Circulating Apoptosis‐ and Autophagy‐Related lncRNAs as Diagnostic Markers in Coronary Artery Disease

Zhang

¹

,

Lou

²

,

He

³

et al. 2021

BioMed Research International

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Objective. Increasing evidence emphasizes the implications of dysregulated apoptosis and autophagy cellular processes in coronary artery disease (CAD). Herein, we aimed to explore apoptosis- and autophagy-related long noncoding RNAs (lncRNAs) in peripheral blood of CAD patients. Methods. The mRNA and lncRNA expression profiles were retrieved from the Gene Expression Omnibus (GEO) database. With ∣ fold change ∣ > 1.5 and adjusted p value < 0.05, differentially expressed apoptosis- and autophagy-related mRNAs were screened between CAD and healthy blood samples. Also, differentially expressed lncRNAs were identified for CAD. Using the psych package, apoptosis- and autophagy-related lncRNAs were defined with Spearson’s correlation analysis. Receiver operating characteristic (ROC) curves were conducted for the assessment of the diagnosed efficacy of these apoptosis- and autophagy-related lncRNAs. Results. Our results showed that 24 apoptosis- and autophagy-related mRNAs were abnormally expressed in CAD than normal controls. 12 circulating upregulated and 1 downregulated apoptosis- and autophagy-related lncRNAs were identified for CAD. The ROCs confirmed that AC004485.3 ( AUC = 0.899 ), AC004920.3 ( AUC = 0.93 ), AJ006998.2 ( AUC = 0.776 ), H19 ( AUC = 0.943 ), RP5-902P8.10 ( AUC = 0.956 ), RP5-1114G22.2 ( AUC = 0.883 ), RP11-247A12.1 ( AUC = 0.885 ), RP11-288L9.4 ( AUC = 0.928 ), RP11-344B5.2 ( AUC = 0.858 ), RP11-452C8.1 ( AUC = 0.929 ), RP11-565A3.1 ( AUC = 0.893 ), and XXbac-B33L19.4 ( AUC = 0.932 ) exhibited good performance in differentiating CAD from healthy controls. Conclusion. Collectively, our findings proposed that circulating apoptosis- and autophagy-related lncRNAs could become underlying diagnostic markers for CAD in clinical practice.

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“…The observed increase in the LVA patient plasma might represent apoptotic activity. Higher circulating levels of caspase-8 were found to associate with increased incidence of cardiovascular events [26]. Several proteins found at higher abundance in LVA patients are involved in transcriptional processes or chromatin remodeling respectively, namely SWI/SNF complex subunit SMARCC1 (SMARCC1), transcription elongation factor SPT6 (SUPT6H), and zinc finger protein 30 homologue (ZFP30).…”

Section: Discussionmentioning

confidence: 99%

Circulating proteomic patterns in AF related left atrial remodeling indicate involvement of coagulation and complement cascade

Kornej

¹

,

Büttner

²

,

Hammer

³

et al. 2018

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BackgroundLeft atrial (LA) electro-anatomical remodeling and diameter increase in atrial fibrillation (AF) indicates disease progression and is associated with poor therapeutic success. Furthermore, AF leads to a hypercoagulable state, which in turn promotes the development of a substrate for AF and disease progression in the experimental setting. The aim of this study was to identify pathways associated with LA remodeling in AF patients using untargeted proteomics approach.MethodsPeripheral blood samples of 48 patients (62±10 years, 63% males, 59% persistent AF) undergoing AF catheter ablation were collected before ablation. 23 patients with left atrial low voltage areas (LVA), defined as <0.5 mV, and 25 patients without LVA were matched for age, gender and CHA2DS2-VASc score. Untargeted proteome analysis was performed using LC-ESI-Tandem mass spectrometry in a label free intensity based workflow. Significantly different abundant proteins were identified and used for pathway analysis and protein-protein interaction analysis.ResultsAnalysis covered 280 non-redundant circulating plasma proteins. The presence of LVA correlated with 30 differentially abundant proteins of coagulation and complement cascade (q<0.05).ConclusionsThis pilot proteomic study identified plasma protein candidates associated with electro-anatomical remodeling in AF and pointed towards an imbalance in coagulation and complement pathway, tissue remodeling and inflammation.

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FADD, Caspase-3, and Caspase-8 and Incidence of Coronary Events

Abstract: High levels of FADD and caspase-8, but not caspase-3, were associated with increased incidence of CE in subjects from the general population. The in vitro experiments support the view that these biomarkers could reflect activation of the extrinsic apoptotic pathway.

Cited by 23 publications

References 30 publications

Differences in Biomarkers of Inflammation Between Novel Subgroups of Recent-Onset Diabetes

Differences in Biomarkers of Inflammation Between Novel Subgroups of Recent-Onset Diabetes

[Retracted] Dysregulated Circulating Apoptosis‐ and Autophagy‐Related lncRNAs as Diagnostic Markers in Coronary Artery Disease

Circulating proteomic patterns in AF related left atrial remodeling indicate involvement of coagulation and complement cascade

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