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Comprehensive identification of RNA transcripts and construction of RNA networks in coronary arterial calcification

ABSTRACT: Here, we report a comprehensive analysis of dysregulated mRNAs, lncRNAs, miRNAs and circRNAs in peripheral blood of CAC patients with high-throughput RNA sequencing. We mapped about 50 million sequence reads per sample to the human genome. GSEA analysis showed that these dysregulated RNAs correlate with several critical biological processes such as RNA modification, and RNA metabolism. RT-qPCR (SYBR Green assays) with more clinical CAC samples were used for the validation of some dysregulated RNAs. We have also constructed the co-expression network between lncRNA and mRNA, and established the circRNA-miRNA-mRNA in CAC based on this data. This study provides valuable insights to understand the RNA involvement and regulation in CAC, assisting future CAC investigations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE194304 | GEO | 2022/07/01

REPOSITORIES: GEO

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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:BACKGROUND:There is increasing evidence that breast arterial calcification (BAC), an incidental finding on 3-29% of mammograms, could be used to screen for coronary artery disease (CAD). We conducted a systematic review to assess the associations between BAC and CAD and its risk factors (hypertension, hypercholesterolemia, diabetes mellitus and smoking). METHODS AND FINDINGS:MEDLINE and EMBASE databases and references of relevant papers were searched up to 18 February 2020 for English language studies that evaluated the associations of BAC and CAD and its risk factors. A single reviewer extracted all data and assessed study quality with verification by another independent reviewer, if required. Across 31 studies (n = 35,583; 3 longitudinal and 28 cross-sectional studies) that examined the association of BAC and CAD, the OR was 2.61 (95% CI 2.12-3.21; I2 = 71%). Sub-analysis of studies that graded BAC severity using the 4- (4 studies) or 12-point scale systems (3 studies) revealed an association with CAD and moderate-severe BAC (OR 4.83 (95%CI 1.50-15.54) and OR 2.95 (95%CI 1.49-5.84), respectively) but not mild BAC (OR 2.04 (95%CI 0.82-5.05) and OR 1.08 (95%CI 0.42-2.75), respectively). BAC was associated with hypertension (42 studies; n = 32,646; OR 1.80; 95% CI 1.47-2.21; I2 = 85%) and diabetes mellitus (51 studies; n = 53,464; OR 2.17; 95% CI 1.82-2.59; I2 = 75%) but not with hypercholesterolemia (OR 1.31; 95%CI 0.97-1.77; I2 = 67%). Smoking was inversely associated with BAC (35 studies; n = 40,002; OR 0.54; 95% CI 0.42-0.70; I2 = 83%). Studies mostly included symptomatic women. Marked heterogeneity existed and publication bias may be present. CONCLUSIONS:BAC is associated with CAD, diabetes mellitus and hypertension and inversely associated with smoking. Whether BAC could screen for CAD cannot be determined from current published data due to the lack of larger prospective studies. A consensus approach to quantifying BAC may also facilitate further translation into clinical care. PROSPERO: CRD42020141644.

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Comprehensive identification of RNA transcripts and construction of RNA networks in coronary arterial calcification

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