Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmonary Hypertension

Calvier, Laurent; Herz, Joachim; Hansmann, Georg

doi:10.1016/j.jacbts.2021.09.011

Cited by 35 publications

(24 citation statements)

References 150 publications

(235 reference statements)

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“…CEACAM1 [340], ACSL1 [341], TLR4 [342], ABCA1 [343], TLR5 [344], CYP2D6 [345], JAK2 [346], NOTCH2 [347], DDX3X [348], NCOA4 [349], EGR1 [350], IQGAP2 [351], GCLC (glutamate-cysteine ligase catalytic subunit) [352], VEGFA (vascular endothelial growth factor A) [353], ITGB1 [354], LDLR (low density lipoprotein receptor) [355], TLR6 [316], SIRT1 [356], FGL2 [357], TET2 [358], PHF2 [328], VEGFB (vascular endothelial growth factor B) [359], SELENOM (selenoprotein M) [360], TRPM4 [361], OLFM2 [362] and ATAD3A [363] are thought to be involved in non-alcoholic fatty liver disease. Altered expression of ATOH8 [364], STAT1 [365], ARG1 [366], TLR4 [367], VNN1 [368], ABCA1 [369], IFIH1 [370], PTGS2 [371], F2RL1 [289], CYP2D6 [372], PDK4 [373], RNF213 [374], JAK2 [375], NOTCH2 [376], PDGFC (platelet derived growth factor C) [377], TLR2 [378], CYP1B1 [379], IL1RN [380], GCH1 [381], EGR1 [382], HIF1A [383], PLA2G7 [384], CCR2 [385], GAB1 [386], VEGFA (vascular endothelial growth factor A) [387], OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [388], OXR1 [389], IRF9 [390], FMR1 [391], LDLR (low density lipoprotein receptor) [392], SIRT1 [393], NOD2 [394], ATP13A3 [395], VCAN (versican) [396], FGL2 [397], TET2 [398], KDM6A [399], KLHL2 [400], CAVIN1 [401], TNFRSF4 [402], PF4 [403], VEGFB (vascular endothelial growth factor B) [330], CCR7 [404], PRDX2 [405], HSPB1 [406], TCF4 […”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Coronary artery disease (CAD) is the most common cardiovascular disorder and the leading cause of heart related deaths in world. Increasing molecular targets have been discovered for CAD and CAD - related complications prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might help the diagnosis and treatment of CAD and CAD related complications. We searched next generation sequencing (NGS) dataset (GSE202625) and identified differentially expressed genes (DEGs) by comparing CAD and normal control samples using DESeq2. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g:Profiler online database. The protein protein interaction (PPI) network was plotted with IMEx interactome and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. MiRNA hub gene regulatory network and TF hub gene regulatory network analysis was performed to identify the hub genes, miRNAs and TFs. Receiver operating characteristic (ROC) curve analysis was used to predict the diagnostic effectiveness of the hub genes. A total of 118 DEGs (479 up regulated genes and 479 down regulated genes) were detected. The GO enrichment analysis indicated that the DEGs most significantly enriched in cellular response to stimulus and biosynthetic process. The REACTOME pathway enrichment analysis revealed that the DEGs were most significantly enriched in immune system and eukaryotic translation elongation. PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network analysis demonstrated that EGR1, SIRT1, STAT1, LRRK2, HIF1A, CSNK2B, RPS3, RPS2, RPS4X and HDAC11 were the hub genes. On the whole, the findings of this study enhance our understanding of the potential molecular mechanisms of CAD and CAD-related complications, and provide potential targets for further research.

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Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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“…However, LRP1B encodes a member of the low-density lipoprotein (LDL) receptor family, which has been extensively studied in atherosclerosis. 39 Although several members of the LDL receptor family have been discovered to play crucial roles in PAH, 40 LRP1B has not yet been directly linked with PAH. However, the role of LRP1B has been studied in vascular smooth muscle cells, and the results showed that LRP1B interacts with platelet-derived growth factor receptor-β, leading to a decrease in ERK1/2 signaling and inhibits cell migration.…”

Section: Discussionmentioning

confidence: 99%

“…However, the role of LRP1B has been studied in vascular smooth muscle cells, and the results showed that LRP1B interacts with platelet-derived growth factor receptor-β, leading to a decrease in ERK1/2 signaling and inhibits cell migration. 40 In addition, the LRP1B genetic polymorphism is correlated with the occurrence of coronary artery aneurysms in Kawasaki disease, which is an acute and systemic vasculitis. 41 These findings suggest the potential involvement of LRP1B in vascular inflammation; however, its functional effects remain to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing Revealed Variants That Predict Pulmonary Artery Involvement in Patients with Takayasu Arteritis

Liu¹,

Chen²,

Li³

et al. 2022

JIR

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To conduct the first whole exome sequencing (WES) on Takayasu arteritis (TAK) to identify common and rare variants responsible for disease susceptibility. Patients and Methods: A total of 200 patients and 1675 healthy controls from China were recruited for this study. Site-based association analysis for common variants and gene-based burden analysis for rare variants were conducted. A weighted genetic risk score (wGRS) was calculated for each patient with TAK based on the independent risk alleles identified in the association analyses. The ability of the patient wGRS to discriminate between different phenotypes was evaluated. Results: In the site-based analysis, the top association signal was CCHCR1 (rs1265067, p = 8.27 × 10 −12 , OR = 2.41), a proxy for HLA-B*52:01. HLA-DQB1 (rs9273902), HLA-DQB2 (rs34109750), and a haplotype block in the human leukocyte antigen (HLA) class III region (represented by rs3130618) also exhibited significant associations independently. In addition, four novel non-HLA susceptibility loci were identified: PRRT4, TLL2, LRP1B, and DLGAP2. Twelve independently associated single nucleotide polymorphisms were used to calculate the wGRS. TAK patients with a higher wGRS were found to have an increased risk of pulmonary artery involvement compared with those with a lower wGRS (p = 5.76 × 10 −7 , OR = 13.92). The wGRS algorithm showed good predictive capability for pulmonary artery involvement in TAK (sensitivity, 92.1%; specificity, 59.9%). In the gene-based analysis, risk genes that reached exome-wide significance were not identified. Conclusion:This WES study on TAK supports a previously reported association within the HLA region. Moreover, novel susceptibility loci were identified outside the HLA region. These risk alleles showed potential associations with pulmonary artery involvement in TAK. However, additional studies are warranted to verify our findings.

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“…In vitro, LOX-1 expression is known to be induced by various cytokines and shear stress [ 39 ]. Interestingly, LOX-1 is rarely expressed in normal vessels but is strongly expressed in endothelial cells, VSMCs and macrophages in atherosclerotic lesions [ 39 , 40 ].…”

Section: Oxidative Stressmentioning

confidence: 99%

Roles of Oxidative Stress and Inflammation in Vascular Endothelial Dysfunction-Related Disease

Higashi

2022

Antioxidants

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Oxidative stress and chronic inflammation play an important role in the pathogenesis of atherosclerosis. Atherosclerosis develops as the first step of vascular endothelial dysfunction induced by complex molecular mechanisms. Vascular endothelial dysfunction leads to oxidative stress and inflammation of vessel walls, which in turn enhances vascular endothelial dysfunction. Vascular endothelial dysfunction and vascular wall oxidative stress and chronic inflammation make a vicious cycle that leads to the development of atherosclerosis. Simultaneously capturing and accurately evaluating the association of vascular endothelial function with oxidative stress and inflammation would be useful for elucidating the pathophysiology of atherosclerosis, determining treatment efficacy, and predicting future cardiovascular complications. Intervention in both areas is expected to inhibit the progression of atherosclerosis and prevent cardiovascular complications.

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Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmonary Hypertension

Cited by 35 publications

References 150 publications

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Whole Exome Sequencing Revealed Variants That Predict Pulmonary Artery Involvement in Patients with Takayasu Arteritis

Roles of Oxidative Stress and Inflammation in Vascular Endothelial Dysfunction-Related Disease

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