Expression Analysis of Leukotriene-Inflammatory Gene Interaction Network in Patients with Coronary Artery Disease

Nair, Jiny; Shanker, Jayashree; Jambunathan, Srikarthika; Arvind, Prathima; Kakkar, Vijay V.

doi:10.5551/jat.20123

Cited by 17 publications

(16 citation statements)

References 45 publications

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“…LTs are lipid mediators that are derived from the 5-lipoxygenase pathway of arachidonic acid metabolism, and which modulate inflammation in pulmonary arterial hypertension ( 32 ). LTs serve a pivotal role in the pathogenesis of atherosclerosis, have a close association with CHD ( 33 ), and additionally increase oxygen free radicals involved in the development and maintenance of heart failure, which is a typical symptom of PHD ( 34 ). Due to the fact that LTs are important in IPAH, CHD and PHD, the use of agents that influence the LT pathway has potential for the use in treatment for IPAH and PHD ( 32 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

“…Due to the fact that LTs are important in IPAH, CHD and PHD, the use of agents that influence the LT pathway has potential for the use in treatment for IPAH and PHD ( 32 , 34 ). LTs have additionally been identified to be effective in predicting CHD ( 33 ). Functional observations including oxidation reduction, the unsaturated fatty acid biosynthetic process, the glycoprotein biosynthetic process and the eicosanoid metabolic process were additionally identified to be associated with IPAH, CHD and PHD in the current study; however, these observations require further investigation and discussion.…”

Section: Discussionmentioning

confidence: 99%

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Deciphering the genetic and modular connections between coronary heart disease, idiopathic pulmonary arterial hypertension and pulmonary heart disease

Yuan

Zhang

et al. 2016

Molecular Medicine Reports

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Coronary heart disease (CHD), idiopathic pulmonary arterial hypertension (IPAH) and pulmonary heart disease (PHD) are circulatory system diseases that may simultaneously emerge in a patient and they are often treated together in clinical practice. However, the molecular mechanisms connecting these three diseases remain unclear. In order to determine the multidimensional characteristic correlations between these three diseases based on genomic networks to aid in medical decision-making, genes from the Online Mendelian Inheritance in Man database were obtained, and applied network construction and modularized analysis were conducted. Functional enrichment analysis was conducted to explore the associations between overlapping genes, modules and pathways. A total of 29 overlapping genes and 3 common modules were identifed for the 3 diseases. Glycosphingolipid biosynthesis and the arachidonic acid metabolism are common pathways, and the biosynthetic process is suggested to be the major function involved in the three diseases. The current study reported, to the best of our knowledge for the first time, the role of glycosphingolipid biosynthesis in IPAH and PHD. The present study provided an improved understanding of the pathological mechanisms underlying CHD, IPAH and PHD. The overlapping genes, modules and pathways suggest novel areas for further research, and drug targets. The observations of the current study additionally suggest that drug indications can be broadened because of the presence of common targets.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Deciphering the genetic and modular connections between coronary heart disease, idiopathic pulmonary arterial hypertension and pulmonary heart disease

Yuan

Zhang

et al. 2016

Molecular Medicine Reports

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“…Selection of candidate genes : The network approach helped identify key inflammatory genes from a large panel of genes involved in the inflammatory process and the direct interactions among the genes in the leukotriene pathway 6 7 . The 18 genes prioritized for the present study are listed in Table II and include the leukotriene pathway genes, inflammatory genes and key transcription factors.…”

Section: Methodsmentioning

confidence: 99%

“…To address this, the expression of a select panel of 18 inflammatory genes was studied in patients with MetS and CAD and the association and correlation patterns of relative gene expression were compared with each other and against controls. These 18 genes were selected based on bioinformatics analysis of the inflammatory bionetwork previously carried out for gene prioritization 6 and through a selection of highly networked leukotriene-induced inflammatory genes described elsewhere 7 .…”

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confidence: 99%

Comparative analysis of inflammatory gene expression levels in metabolic syndrome & coronary artery disease

2017

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Background & objectives:Metabolic syndrome (MetS) increases the likelihood of developing coronary artery disease (CAD), and inflammation is involved in the pathogenesis of both these conditions. The present work was conducted to examine the relative expression of 18 key inflammatory genes associated with MetS and incident CAD in a representative group of patients.Methods:A total of 178 male patients, including 57 with CAD and 121 without CAD, were enrolled in the study. The participants without CAD were characterized for the presence of MetS using modified criteria specific for Asian Indians, which included a lower cut-off for waist circumference (≥90 cm for men). The expression of 18 inflammatory genes was evaluated in peripheral whole blood by quantitative polymerase chain reaction method.Results:Of the 121 participants without CAD, 53 (43.8%) had three or more risk factors (MetS group), 50 (41.3%) had one or two risk factors (non-MetS group), while 18 (14.8%) did not have any risk factors (control group). High nuclear factor-kappa B (NF-κB) expression levels and low interleukin-10 (IL-10) levels were observed in MetS patients. Linear association was seen between NF-κB and vascular endothelial growth factor A (VEGFA) expression and with increase in MetS components. Comparison of gene expression pattern between CAD and MetS revealed significantly higher expression of leukotriene genes - arachidonate 5-lipoxygenase (ALOX5), arachidonate 5-lipoxygenase activating protein (ALOX5 AP), leukotriene A4 hydrolase (LTA4H) and leukotriene C4 synthase (LTC4S), and lower expression of NF-κB, interleukin 1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1/CCL2) and signal transducer and activator of transcription 3 (STAT3) genes in CAD. There was linear increase in expression of LTA4H, LTC4S, IL-8 and VEGFA genes across the four groups, namely from controls, non-MetS, MetS and CAD.Interpretation & conclusions:A distinct gene expression pattern was seen in MetS and CAD implying a well-orchestrated inflammatory and immune activity. Specifically, NF-κB might be playing an active role in MetS, allowing further expansion of the inflammatory process with resolution of inflammation in full-blown CAD, wherein other gene players such as leukotrienes may dominate.

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“…IL-8 production remains elevated for an extended period during acute inflammation, whereas other inflammatory cytokines are cleared within a few hours (DeForge et al, 1992;Shebuski and Kilgore, 2002). Liu et al (1997) suggested that IL-8 contributes to the recruitment of T lymphocytes and smooth muscle cells to the subendothelial space and has a major role in the formation of atherosclerotic lesions, whereas Nair et al (2014) showed that IL-8 gene expression is a predictor of cardiovascular risk. Therefore, IL-8 may play a role in the pathogenesis of atherosclerosis, and thus appears to be associated with the development of CAD.…”

Section: Discussionmentioning

confidence: 99%

IL-8 -251A/T polymorphism contributes to coronary artery disease susceptibility in a Chinese population

Zhang

et al. 2017

Genet. Mol. Res.

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ABSTRACT. ) is a mediator of inflammation and plays an important role in regulating immune responses. To date, several studies have tested the association between IL-8 gene polymorphisms and development of coronary artery disease (CAD), but their results have proved to be inconsistent. We conducted an investigation to assess the relationship between the IL-8 -251A/T (rs4073) sequence variant and CAD in a Chinese population. Between April 2013 and January 2015, 217 patients with coronary angiography-confirmed CAD were enrolled in our study, along with 245 control subjects. IL-8 -251A/T genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism assay. A chi-square test revealed that IL-8 -251A/ T genotype distributions significantly differed between CAD patients and control subjects (chi-square = 8.29, P < 0.02). Moreover, multiplelogistic regression analysis showed that individuals carrying TA [odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.01-2.57] and AA (OR = 2.06, 95%CI = 1.21-3.52) genotypes were at increased risk of CAD compared to those with the TT genotype. Under dominant (OR = 1.75, 95%CI = 1.13-2.73) and recessive (OR = 1.54, 95%CI = 1.02-2.37) genetic models, the IL-8 -251A/T polymorphism also significantly correlated with CAD. In conclusion, our results suggest that this variant is an independent risk factor for CAD development under codominant, dominant, and recessive models.

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Expression Analysis of Leukotriene-Inflammatory Gene Interaction Network in Patients with Coronary Artery Disease

Cited by 17 publications

References 45 publications

Deciphering the genetic and modular connections between coronary heart disease, idiopathic pulmonary arterial hypertension and pulmonary heart disease

Deciphering the genetic and modular connections between coronary heart disease, idiopathic pulmonary arterial hypertension and pulmonary heart disease

Comparative analysis of inflammatory gene expression levels in metabolic syndrome & coronary artery disease

IL-8 -251A/T polymorphism contributes to coronary artery disease susceptibility in a Chinese population

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