Dataset Information

NALP3-Inflammasome-Related Gene Polymorphisms in Patients with Prehypertension and Coronary Atherosclerosis.

ABSTRACT: Objectives. Prehypertension is an early stage of hypertension that is characterized by inflammatory factors. Inflammation also plays an essential role in the development of coronary atherosclerosis (CAS). The present study evaluated the NALP3-inflammasome and its related genes, NLRP3, NOD2, and CARD8, using SNP linkage and gene haplotypes in prehypertensive patients. Methods. A total of 576 patients with prehypertension and suspected coronary heart disease (CHD) were enrolled. According to coronary angiography, patients were divided into two groups: arterial stenosis <50% of the diameter (control) and arterial stenosis >50% of the diameter (case). Fifteen polymorphisms in the NOD2, NLRP3, and CARD8 genes were analyzed, and serum levels of C-reactive protein (CRP) were measured. Results. When comparing allele frequencies, none of these 15 SNPs in NOD2, CARD8, and NLPR3 genes showed a significant difference using multiple logistic regression. However, the CTACATAA (p = 0.0064) and CCACATAG (p = 0.0126) haplotypes of the NOD2 gene SNPs were significantly different between cases and controls. Conclusions. Although our study excludes a significant association of selected SNPs in these genes with CHD in prehypertension patients, this work suggests that the CTACATAA and CCACATAG haplotypes were associated with CHD in the NOD2 locus. This work suggests that the CTACATAA and CCACATAG haplotypes were associated with CHD in prehypertension patients in the NOD2 locus.

SUBMITTER: Zhao X

PROVIDER: S-EPMC4944040 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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NALP3-Inflammasome-Related Gene Polymorphisms in Patients with Prehypertension and Coronary Atherosclerosis.

Zhao Xin X Gu Chonghuai C Yan Chenghui C Zhang Xiaolin X Li Yi Y Wang Li L Ren Lili L Zhang Yan Y Peng Junyin J Zhu Zhiming Z Han Yaling Y Han Yaling Y

BioMed research international 20160630

Objectives. Prehypertension is an early stage of hypertension that is characterized by inflammatory factors. Inflammation also plays an essential role in the development of coronary atherosclerosis (CAS). The present study evaluated the NALP3-inflammasome and its related genes, NLRP3, NOD2, and CARD8, using SNP linkage and gene haplotypes in prehypertensive patients. Methods. A total of 576 patients with prehypertension and suspected coronary heart disease (CHD) were enrolled. According to coron ...[more]

PMID: 27446957

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Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Project description:Backgrounds and Aims: Na+ is an important nutrient and its intake, mainly from salt (NaCl), is essential for normal physiological function. However, high salt intake may lead to vascular injury, independent of a rise in blood pressure (BP). Canonical NALP3 inflammasome activation is a caspase-1 medicated process, resulting in the secretion of IL-18 and IL-1β which lead to endothelial dysfunction. However, some researches uncovered a direct and inflammasome-independent role of NALP3 in renal injury. Thus, this study was designed to investigate the possible mechanisms of NALP3 in high salt induced endothelial dysfunction. Methods and Results: Changes in endothelial function were measured by investigating mice (C57BL/6J, NALP3-/- and wild-type, WT) fed with normal salt diet (NSD) or high salt diet (HSD) for 12W, and thoracic aortic rings from C57BL/6J mice cultured in high-salt medium. Changes of tube formation ability, intracellular reactive oxygen species (ROS), and NALP3 inflammasome expression were detected using mouse aortic endothelial cells (MAECs) cultured in high-salt medium. Consumption of HSD for 12W did not affect BP or body weight in C57BL/6J mice. Endothelium-dependent relaxation (EDR) decreased significantly in C57BL/6J mice fed with HSD for 12W, and in isolated thoracic aortic rings cultured in high-salt medium for 24 h. Results from the aortic ring assay also revealed that the angiogenic function of thoracic aortas was impaired by either consumption of HSD or exposure to high-salt medium. NALP3-/- mice fed with HSD showed a relatively mild decrease in EDR function when compared with WT mice. Tube length of thoracic aortic rings from NALP3-/- mice was longer than those from WT mice after receiving high-salt treatment. Inhibiting NALP3 with a NALP3 antagonist, small interfering (si) RNA experiments using si-NALP3, and decomposing ROS significantly improved tube formation ability in MAECs under high salt medium. NALP3 expression was increased in MAECs cultured with high salt treatment and inhibiting NALP3 reversed the down-regulation of p-eNOS induced by high salt in MAECs. Conclusion: High salt intake impairs endothelial function, which is at least in part mediated by increasing NALP3 expression.

Dataset Information

NALP3-Inflammasome-Related Gene Polymorphisms in Patients with Prehypertension and Coronary Atherosclerosis.

Publications

NALP3-Inflammasome-Related Gene Polymorphisms in Patients with Prehypertension and Coronary Atherosclerosis.

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