Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks

Andújar-Vera, Francisco; Ferrer-Millán, María; García-Fontana, Cristina; García-Fontana, Beatriz; González-Salvatierra, Sheila; Torre, Raquel Sanabria-de la; Martínez-Heredia, Luis; Riquelme-Gallego, Blanca; Muñóz-Torres, Manuel

doi:10.3390/ijms24044124

Cited by 4 publications

(11 citation statements)

References 105 publications

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“…Together with PPARγ, CEBPA regulates the adipogenesis process and is involved in the sequence expression of adipocytespecific proteins [30][31][32][33][34][35][36]. CEBPA is upregulated in unstable plaques, and overexpression of CEBPA may contribute to the occurrence and development of atherosclerosis [37,38]. However, Bristol et al [39] observed that CEBPA and CEBPB bind the TNFR1 promoter, increase its expression through a positive feedback mechanism, and induce an increase in TNF expression.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-based identification and validation of hub genes associated with aging in patients with coronary artery disease

Zhang,

Zhao,

Xin

et al. 2023

Aging

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Coronary artery disease (CAD) is the most common aging-related disease in adults. We used bioinformatics analysis to study genes associated with aging in patients with CAD. The microarray data of the GSE12288 dataset were downloaded from the Gene Expression Omnibus database to obtain 934 CAD-associated differentially expressed genes. By overlaying them with aging-related genes in the Aging Atlas database, 33 differentially expressed aging-related genes (DEARGs) were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the 33 DEARGs were mainly enriched in cell adhesion and activation, Th17 and Th1/Th2 cell differentiation, and longevity regulation pathways. Hub genes were further screened using multiple algorithms of Cytoscape software and validation set GSE71226. Clinical samples were then collected, and the expression of hub genes in whole blood was detected by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot at the transcription and translation levels. Finally, HSP90AA1 and CEBPA were identified as hub genes. The results of this study suggest that HSP90AA1 and CEBPA are closely related to CAD. These findings provide a theoretical basis for the association between aging effectors and CAD, and indicate that these genes may be promising biomarkers for the diagnosis and treatment of CAD.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics-based identification and validation of hub genes associated with aging in patients with coronary artery disease

Zhang,

Zhao,

Xin

et al. 2023

Aging

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“…Il-1β and Il-6 are two important pro-inflammatory cytokines that amplify inflammation and sensitize hepatocytes to TNF-induced liver damage [43]. ADAMTS1, a metalloproteinase belonging to the ADAMS family, is involved in extracellular matrix (ECM) remodeling [44]. Several studies suggest a link between ADAMTS1 not only with the development of atherosclerotic plaques and ATH [45] but also with the ability to activate hepatic fibrotic TGF-b [46].…”

Section: Discussionmentioning

confidence: 99%

High-Carbohydrate Diet Consumption Poses a More Severe Liver Cholesterol Deposition than a High-Fat and High-Calorie Diet in Mice

Zhang,

Li,

Liu

et al. 2023

IJMS

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In the past few decades, many researchers believed that a high-fat and high-calorie diet is the most critical factor leading to metabolic diseases. However, increasing evidence shows a high-carbohydrate and low-fat diet may also be a significant risk factor. It needs a comprehensive evaluation to prove which viewpoint is more persuasive. We systematically compared the effects of high-fat and high-calorie diets and high-carbohydrate and low-fat ones on glycolipid metabolism in mice to evaluate and compare the effects of different dietary patterns on metabolic changes in mice. Sixty 8-week-old male C57BL/6 mice were divided into four groups after acclimatization and 15% (F-15), 25% (F-25), 35% (F-35), and 45% (F-45) of their dietary energy was derived from fat for 24 weeks. The body weight, body-fat percentage, fasting blood glucose, lipid content in the serum, and triglyceride content in the livers of mice showed a significantly positive correlation with dietary oil supplementation. Interestingly, the total cholesterol content in the livers of mice in the F-15 group was significantly higher than that in other groups (p < 0.05). Compared with the F-45 group, the mRNA expression of sterol synthesis and absorption-related genes (e.g., Asgr1, mTorc1, Ucp20, Srebp2, Hmgcr, and Ldlr), liver fibrosis-related genes (e.g., Col4a1 and Adamts1) and inflammation-related genes (e.g., Il-1β and Il-6) were significantly higher in the F-15 group. Compared with the F-45 group, the relative abundance of unclassified_f_Lachnospiraceae and Akkermansia was decreased in the F-15 group. While unclassified_f_Lachnospiraceae and Akkermansia are potentially beneficial bacteria, they have the ability to produce short-chain fatty acids and modulate cholesterol metabolism. In addition, the relative abundance of unclassified_f_Lachnospiraceae and Akkermansia was significantly positively correlated with fatty acid transporters expression and negatively correlated with that of cholesteryl acyltransferase 1 and cholesterol synthesis-related genes. In conclusion, our study delineated how a high-fat and high-calorie diet (fat supplied higher than or equal to 35%) induced obesity and hepatic lipid deposition in mice. Although the high-carbohydrate and low-fat diet did not cause weight gain in mice, it induced cholesterol deposition in the liver. The mechanism is mainly through the induction of endogenous synthesis of cholesterol in mice liver through the ASGR1-mTORC1-USP20-HMGCR signaling pathway. The appropriate oil and carbon water ratio (dietary energy supply from fat of 25%) showed the best gluco-lipid metabolic homeostasis in mice.

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“…Pie charts were used to compare the proportions of elements, and to visualise their percentages (Figure 2). Elements such as 44 Ca, potassium ( 39 K), sodium ( 23 Na), 31 P, magnesium ( 24 Mg), zinc ( 66 Zn), and 56 Fe, which were present in the highest concentration, were removed from the graph to show the proportions of trace elements in the tissues examined. The series for both organs was split at 140 ppb.…”

Section: Mineral Status Of the Investigated Tissues Based On Icp-ms M...mentioning

confidence: 99%

“…A key role in the initiation of ATH is played by damage to the arterial endothelial cells by reactive oxygen and nitrogen species (ROS and RNS). These are generated by mitochondrial dysfunction in fatty hepatocytes and the vascular smooth muscle cell (VSMC) proliferation, induced by an overexpression of the coagulation factors angiotensin II [44,45], FII, FX, and FXII [46][47][48], and the production of pro-inflammatory IL-1β and TNF-α, under the influence of ox-LDL, as a consequence of atherogenic dyslipidaemia. Smaller, denser particles, sdLDLs, formed from very low-density lipoproteins (VLDLs), are also involved in the formation of atherogenic plaques.…”

Section: Introductionmentioning

confidence: 99%

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Linking Metallic Micronutrients and Toxic Xenobiotics to Atherosclerosis and Fatty Liver Disease—Postmortem ICP-MS Analysis of Selected Human Tissues

et al. 2023

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Dyslipidaemia is a disorder of the lipid metabolism, caused mainly by poor eating habits. The most severe consequence of an inappropriate diet is the development of atherosclerosis and hepatic steatosis. It is generally believed that a change in nutrition, and increased physical activity can eliminate these health problems. The contemporary research and therapies used to treat dyslipidemia mainly focus on lowering the triglyceride and cholesterol levels. However, disturbances in trace element homeostasis or the accumulation of toxic elements can also affect physiological processes, and be involved in the development of metabolically mediated diseases. The present study aimed to determine the mineral profiles of liver and brain tissues collected at autopsy (n = 39) in groups of people with hepatic steatosis (n = 5), atherosclerosis (n = 9), hepatic steatosis, and atherosclerosis (n = 16), and others without the selected disorders (n = 9). Concentrations of 51 elements were analysed via inductively coupled plasma mass spectrometry (ICP-MS) after the initial wet mineralisation of the samples with nitric acid. The results obtained allow us to conclude that the hepatic steatosis group suffers from a deficiency of important trace elements, such as copper, zinc, and molybdenum (p < 0.05), whereas the group with atherosclerosis is characterised by elevated levels of cadmium in the liver tissue (p = 0.01). Analysing the mean values of the element concentrations measured in 11 brain areas, statistically significant higher levels of calcium and copper (p < 0.001) were found in the atherosclerosis group, compared to the hepatic steatosis group, confirming the involvement of these elements in the pathogenesis of atherosclerosis. In addition, an accumulation of cadmium, lead, titanium, and strontium in the brain tissue was observed in the atherosclerosis group. While the accumulation of individual elements differs in different parts of the brain, the differences in the cadmium content (p < 0.05) between the study groups apply to the whole brain, except for the nucleus accumbens septi area, where a statistically significant titanium accumulation occurs in the atherosclerosis and steatosis groups, compared to the others (p < 0.05). In addition, the disruption of elemental homeostasis in the brain of a single case with bipolar disorder, and a case with hip replacement was observed. Our results confirm the involvement of chemical elements in the pathogenesis of selected metabolic diseases, and the need for further studies in larger populations.

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Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks

Cited by 4 publications

References 105 publications

Bioinformatics-based identification and validation of hub genes associated with aging in patients with coronary artery disease

Bioinformatics-based identification and validation of hub genes associated with aging in patients with coronary artery disease

High-Carbohydrate Diet Consumption Poses a More Severe Liver Cholesterol Deposition than a High-Fat and High-Calorie Diet in Mice

Linking Metallic Micronutrients and Toxic Xenobiotics to Atherosclerosis and Fatty Liver Disease—Postmortem ICP-MS Analysis of Selected Human Tissues

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