Polymorphic variants of Caspase genes (8 &amp; 3) in the risk prediction of Coronary Artery Disease

Gundapaneni, Kishore Kumar; Shyamala, Nivas; Galimudi, Rajesh Kumar; Kupsal, Keerthi; Gantala, Srilatha Reddy; Padala, Chiranjeevi; Gunda, Padma; Tupurani, Mohini Aiyengar; Puranam, Kaushik; Sahu, Sushanta Kumar; Hanumanth, Surekha Rani

doi:10.1016/j.gene.2017.06.035

“…Of them, silencing CAPN2 suppresses NF-κB activation as well as decreases myocardial infarction remodeling [33]. 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].…”

Section: Discussionmentioning

confidence: 99%

“…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]. H1F1A is significantly altered in CAD patients compared to controls [28].…”

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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“…Single nucleotide polymorphisms (SNPs) influence the expression or the activities of caspase enzymes. Several CASP genes polymorphisms have been found to be associated with kinds of cancers [17–21] and autoimmune inflammatory diseases, such as rheumatoid arthritis [5], coronary artery disease [22], Kawasaki disease [23], acute pancreatitis [24], and ischemic stroke [25], but the relationship with psoriasis has not been studied. And gene expression profiles showed significant differences in the expression of CASP7 and CASP8 between psoriatic lesions and psoriatic nonlesions.…”

Section: Introductionmentioning

confidence: 99%

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China

Yao

¹

,

Hao

²

,

Pei

³

2019

BioMed Research International

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Background. Abnormal apoptosis of keratinocytes is one of the pathological changes of psoriasis. Caspases (CASPs) are the central engines of apoptosis. Studies to date have shown that some SNPs alter the expression of related genes and lead to changes in disease risk. However, no studies have investigated the associations between gene polymorphisms and the risk of psoriasis in Han population in northeast China. Therefore, we conducted a case-control study to explore this question in Han population of northeastern China. Methods. 540 patients with PsV and 612 healthy age- and sex-matched controls were enrolled in this study. We determined the genotypes of 17 single nucleotide polymorphisms (SNPs) from 11 genes of caspase family by the improved multiplex ligation detection reaction (iMLDR) method. A model-based single SNP frequentist test and haplotype association studies were performed to evaluate the association between SNPs and PsV. Results. In the single SNP tests, rs6704688 in CASP8 was significantly associated with psoriasis vulgaris (PsV) in Han population of northeastern China (P = 0.0169, P’ = 0.0179 under the additive model; P = 0.0126, P’ = 0.0149 under the heterozygous model). In haplotype analyses, the CASP7 haplotype GC was found to be associated with PsV risk (case group versus control group, 47.2% versus 54.4%, respectively, p = 0.0149). Conclusions. Our study presented that the gene polymorphisms of CASP7 and CASP8 were significantly associated with PsV in Han population of northeastern China, which implied the functional relationship between PsV and caspase genes. CASP8 and CASP7 SNPs could be new potential biomarkers for risk stratification and prevention of PsV.

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“…CASP3, as one of the most concerned proteins in caspase family, can catalyze the specific cleavage of a variety of key cell proteins, which is one of the most critical apoptotic protease in the process of apoptosis ( Miura, 2011 ). Activation of caspase-3 is a common ultimate signal in response to factors that induce apoptosis, such as plays an important role in the apoptosis of cardiomyocytes ( Gundapaneni et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Investigation and Experimental Exploration of the Antiapoptotic Mechanism of Colchicine on Myocardial Ischemia Reperfusion Injury

Tang

¹

,

Shi

²

,

Qin³

et al. 2021

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Background: The beneficial effects of colchicine on cardiovascular disease have been widely reported in recent studies. Previous research demonstrated that colchicine has a certain protective effect on ischemic myocardium and has the potential to treat myocardial ischemia reperfusion injury (MIRI). However, the potential targets and pharmacological mechanism of colchicine to treat MIRI has not been reported.Methods: In this study, we used network pharmacology and experimental verification to investigate the pharmacological mechanisms of colchicine for the treatment of MIRI. Potential targets of colchicine and MIRI related genes were screened from public databases. The mechanism of colchicine in the treatment of MIRI was determined by protein-protein interaction (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Additionally, we evaluated the effect of colchicine on H9C2 cell activity using CCK-8 assays, observed the effect of colchicine on H9C2 cell apoptosis via flow cytometry, and further verified the expression of key targets after colchicine treated by Western blot.Results: A total of 626 target genes for colchicine and 1549 MIRI disease targets were obtained. 138 overlapping genes were determined as potential targets of colchicine in treating MIRI. the PPI network analysis demonstrated that the targets linked to MIRI were ALB, TNF, ACTB, AKT1, IL6, TP53, IL1B, CASP3 and these targets showed nice affinity with colchicine in molecular docking experiments. The results of GO analysis and KEGG pathway enrichment demonstrated that the anti-MIRI effect of colchicine involves in apoptotic signaling pathway. Further tests suggested that colchicine can protect H9C2 cell from Hypoxia/Reoxygenation (H/R) injury through anti-apoptotic effects. Western blot results demonstrated that colchicine can inhibited MIRI induced apoptosis of H9C2 cell by enhancing the decreased levels of Caspase-3 in myocardial injure model induced by H/R and activating the PI3K/AKT/eNOS pathway.Conclusions: we performed network pharmacology and experimental evaluation to reveal the pharmacological mechanism of colchicine against MIRI. The results from this study could provide a theoretical basis for the development and clinical application of colchicine.

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Polymorphic variants of Caspase genes (8 & 3) in the risk prediction of Coronary Artery Disease

Cited by 7 publications

References 21 publications

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

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

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China

Network Pharmacology-Based Investigation and Experimental Exploration of the Antiapoptotic Mechanism of Colchicine on Myocardial Ischemia Reperfusion Injury

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