scholarly journals Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis

Author(s):  
E. V. Shakhtshneider ◽  
D. E. Ivanoshchuk ◽  
Yu. I. Ragino ◽  
V. S. Fishman ◽  
Ya. V. Polonskaya ◽  
...  

Aim. The goal of the study was to analyze the differential expression of lipid metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis.Material and Methods. The study was performed on the specimens of atherosclerotic plaques in 45–65-year-old patients with coronary atherosclerosis with stable exertional angina functional class II-IV without acute coronary syndrome. Coronary atherosclerosis was verified by coronary angiography. Atherosclerotic plaque tissue was sampled intraoperatively when indicated. Whole-genome sequencing of ribonucleic acid (RNA) was performed using the TruSeq RNA Sample Preparation Kit (Illumina, USA).Results. We analyzed the differences in the expression of 12 genes including LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, ABCA1, APOA1, APOE, LPL, SCARB1, and SREBF2 depending on the type of atherosclerotic plaques. The expression level of APOE gene was eight times higher in unstable atherosclerotic plaques of dystrophic-necrotic type (p < 0.0001). The expression levels of LDLR and APOB genes were eight times higher in stable atherosclerotic plaques (p < 0.0001). We did not find differences in the expression levels of the ABCG5, ABCG8, APOC3, CETP, CLPS, CYP7A1, and PNPLA5 genes.Conclusion. The study showed the differences in the activity of individual metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis. Obtained data may become the basis for the development of test systems aimed at predicting the development of atherosclerotic process and its complications.

2019 ◽  
Author(s):  
Shuaibin Lian ◽  
Yongjie Zhou ◽  
Zixiao Liu ◽  
Andong Gong ◽  
Lin Cheng

Abstract Backgroud: Theoretically, paralogous genes generated through whole genome duplications should share identical expression levels due to their identical sequences and chromatin environments. However, functional divergences and expression differences have arisen due to selective pressures and evolutional stresses. A comprehensive investigation of the expression patterns of paralogous gene pairs in response to various stresses and a study of correlations between the expression levels and sequence divergences of the paralogs are needed. Results: In this study, we analyzed the expression patterns of paralogous genes under different types of stress and investigated the correlations between the expression levels and sequence divergences of the paralogs. Firstly, we analyzed the differential expression patterns of the paralogs under four different types of stress (drought, cold, infection, and herbivory) and classified them into three types according to their expression patterns. Secondly, we further analyzed the differential expression patterns under various degrees of stress and constructed the corresponding co-expression networks of differentially expressed paralogs and transcription factors. Thirdly, we investigated the correlations between the expression levels and sequence divergences of the paralogs and identified positive correlations between expression level and sequence divergence. With regard to the sequence divergence, we identified correlations between selective pressure and phylogenetic relationship. Conclusions: These results shed light on differential expression patterns of paralogs in response to environmental stresses and are helpful for understanding the relations between expression levels and sequences divergences.


2020 ◽  
Author(s):  
Shuaibin Lian ◽  
Yongjie Zhou ◽  
Zixiao Liu ◽  
Andong Gong ◽  
Lin Cheng

Abstract Background Theoretically, paralogous genes generated through whole genome duplications should share identical expression levels due to their identical sequences and chromatin environments. However, functional divergences and expression differences have arisen due to selective pressures throughout evolution. A comprehensive investigation of the expression patterns of paralogous gene pairs in response to various stresses and a study of correlations between the expression levels and sequence divergences of the paralogs are needed. Results In this study, we analyzed the expression patterns of paralogous genes under different types of stress and investigated the correlations between the expression levels and sequence divergences of the paralogs. We analyzed the differential expression patterns of the paralogs under four different types of stress (drought, cold, infection, and herbivory) and classified them into three main types according to their expression patterns. We then further analyzed the differential expression patterns under various degrees of stress and constructed corresponding co-expression networks of differentially expressed paralogs and transcription factors. Finally, we investigated the correlations between the expression levels and sequence divergences of the paralogs and identified positive correlations between expression level and sequence divergence. With regard to sequence divergence, we identified correlations between selective pressures and phylogenetic relationships. Conclusions These results shed light on differential expression patterns of paralogs in response to environmental stresses and are helpful for understanding the relationships between expression levels and sequences divergences.


2019 ◽  
Author(s):  
Shuaibin Lian ◽  
Yongjie Zhou ◽  
Zixiao Liu ◽  
Andong Gong ◽  
Lin Cheng

Abstract Background Theoretically, paralogous genes generated through whole genome duplications should share identical expression levels due to their identical sequences and chromatin environments. However, functional divergences and expression differences have arisen due to selective pressures and evolutional stresses. A comprehensive investigation of the expression patterns of paralogous gene pairs in response to various stresses and a study of correlations between the expression levels and sequence divergences of the paralogs are needed.Results In this study, we analyzed the expression patterns of paralogous genes under different types of stress and investigated the correlations between the expression levels and sequence divergences of the paralogs. Firstly, we analyzed the differential expression patterns of the paralogs under four different types of stress (drought, cold, infection, and herbivory) and classified them into three types according to their expression patterns. Secondly, we further analyzed the differential expression patterns under various degrees of stress and constructed the corresponding co-expression networks of differentially expressed paralogs and transcription factors. Thirdly, we investigated the correlations between the expression levels and sequence divergences of the paralogs and identified positive correlations between expression level and sequence divergence. With regard to the sequence divergence, we identified correlations between selective pressure and phylogenetic relationship.Conclusions These results shed light on differential expression patterns of paralogs in response to environmental stresses and are helpful for understanding the relations between expression levels and sequences divergences.


Author(s):  
Sidney D. Kobernick ◽  
Edna A. Elfont ◽  
Neddra L. Brooks

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
D. Serrano ◽  
J. A. Crookshank ◽  
B. S. Morgan ◽  
R. W. Mueller ◽  
M.-F. Paré ◽  
...  

Abstract In a previous study we reported that prediabetic rats have a unique gene signature that was apparent even in neonates. Several of the changes we observed, including enhanced expression of pro-inflammatory genes and dysregulated UPR and metabolism genes were first observed in the liver followed by the pancreas. In the present study we investigated further early changes in hepatic innate immunity and metabolism in two models of type 1 diabetes (T1D), the BBdp rat and NOD mouse. There was a striking increase in lipid deposits in liver, particularly in neonatal BBdp rats, with a less striking but significant increase in neonatal NOD mice in association with dysregulated expression of lipid metabolism genes. This was associated with a decreased number of extramedullary hematopoietic clusters as well as CD68+ macrophages in the liver of both models. In addition, PPARɣ and phosphorylated AMPKα protein were decreased in neonatal BBdp rats. BBdp rats displayed decreased expression of antimicrobial genes in neonates and decreased M2 genes at 30 days. This suggests hepatic steatosis could be a common early feature in development of T1D that impacts metabolic homeostasis and tolerogenic phenotype in the prediabetic liver.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S El-Deek ◽  
A.R Meki ◽  
A Hassan ◽  
M Gaber ◽  
O Mohamed

Abstract Introduction Acute coronary syndrome (ACS) is a leading cause of mortality and morbidity worldwide. Despite being the gold standard biomarkers, cTn and CK-MB have a major drawback as they are less sensitive in the first 3 hours of the onset of symptom. So, there is still a need for novel biomarkers, which can reliably rule in or rule out this disease immediately on admission. Aim of the work To evaluate the role of copeptin, miRNA-499 and miRNA-208 as novel biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) Patients and Methods: A total of 65 patients presenting within 4 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 23 UA, 42 NSTEMI. Also 25 apparently healthy controls were included. Blood samples (first set within the first 3 hours and second set at 6 hours) were taken for estimation of copeptin by ELISA and miRNA-499 and miRNA-208 expression levels by real time PCR. Results Copeptin, miRNA-499 and miRNA-208 expression levels were significantly increased in UA and NSTEMI patients compared to controls (P&lt;0.001 each). Also these biomarkers were significantly increased in NSTEMT compared to UA (P&lt;0.001 each). They also significantly elevated in UA and NSTEMI patient in the first 3 hours who had negative cardiac troponin (p&lt;0.001 each). ROC curve analysis revealed that the area under curve (AUC) for prediction of ACS was 0.96 for copeptin, 0.97 for miRNA-499 and 0.0.97 for miRNA-208. Interestingly, combining copeptin with miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.98, P&lt;0.001. The sensitivity and specificity within the first 3 hours were 90%, 86% for copeptin, 95%, 94% for miRNA-499 and 93%, 98% for miRNA-208. The sensitivity and specificity were 81% and 86% for cardiac troponin within 6 hours. There was a positive correlation between copeptin and miRNA-499 and miRNA-208 (r=0.75, P&lt;0.001 and r=0.76, P&lt;0.001 respectively) Also, there was a positive correlation between these biomarkers and cTn (r=0.7. P&lt;0.001, r=0.64, P&lt;0.001 and r=0.68, P&lt;0.001 respectively). Conclusions Copeptin, miRNA-499 and miRNA-208 expression might be novel biomarkers as they are associated with UA and NSTEMI presented in the first 3 hours of onset of pain. The combination of copeptin and miRNA with cTn accelerate the diagnosis of ACS and avoiding the gray zone of cTn. Copeptin and miRNAs representing a potential aid in early diagnosis as they have different pathogenesis and site of liberation. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.


Author(s):  
Yanbing Li ◽  
Yu Geng ◽  
Boda Zhou ◽  
Xuejiao Wu ◽  
Ou Zhang ◽  
...  

AbstractIt is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.


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