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Clustering heatmap of the significant proteins in comparison of CAL – control. If the number of proteins to be shown exceeds a specific value, no protein names would be drawn. Missed values are indicated with '–'. The group of control and CAL has three repeats, respectively.
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Vascular calcification (VC) is a pathological process characterized by abnormal deposition of calcium phosphate, hydroxyapatite and other mineral substances in the vascular wall. Hyperphosphorus is an important risk factor associated with VC in the general population and patients with chronic kidney disease (CKD). However, there is still a lack of...
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Objective: Recently, abundant number of studies have revealed many functions of circular RNAs in multiple diseases, however, the role of circular RNA in the rupture of human intracranial aneurysm is still unknown. This study aims to explore the potential functions of circular RNA in the rupture of human intracranial aneurysms.
Methods: The differen...
Background: CircRNAs have been found to play a crucial role in the pathological process of various kinds of diseases. However, the role of circRNAs in the formation and rupture of intracranial aneurysm is still unknown.
Methods: Differentially expressed circRNAs profiles between superficial temporal arteries ( n = 5) and intracranial aneurysms ( n...
Citations
... 7 Existing evidence indicated SWI/SNF complex is a key regulator of the chromatin-remodeling events that promote tissuespecific transcription in osteoblasts, 8 and can regulate certain osteogenic factors including runt-related transcription factor 2 (Runx2), receptor activator of NF-kB ligand (Rankl), and osteocalcin. 8,9 Our previous in vitro study found BRG1was significantly up-regulated in vascular calcification in CKD setting, 10 yet the underlying mechanism is still to be investigated. ...
... 38 Therefore, we examined both rat models in this study and the two models yielded consistent results. The vascular calcification phenotypes of both models were confirmed in a previous report 10 and by the Von Kossas staining results in this study ( Figure S3). Second, the in vivo validation of BRG1 did not include BRG1 conditional knockout rat experiments, which is also our next step to further clarify the function and underlying mechanisms of BRG1 in vascular calcification. ...
We aimed to investigate the mechanisms of Brahma related gene 1 (BRG1) in promoting vascular calcification in chronic kidney disease (CKD). The expression of BRG1 was examined in high phosphorus stimulated rat aortic smooth muscle cells (RASMCs) and calcified artery tissues from rat models and hemodialysis patients. Autophagosome formation was measured in high phosphorus stimulated RASMCs with and without BRG1 knock-down. We also detected the coexistence of BGR1 and exosomes, and measured the circulatory levels of BRG1 in the hemodialysis patients. BRG1 promoted the osteogenic transdifferentiation of RASMCs. Silencing BRG1 prevented autophagy from being induced by high phosphorus stimulation in RASMCs. Increased expression of BRG1 was observed in calcified blood vessels. Serum BRG1 level increased in the hemodialysis patients. BRG1 was involved in the development of high phosphorus induced osteogenic phenotype in vitro and in vivo, and its underlying mechanism might be facilitating autophagy.
... Cells were cultured in Dulbecco's modified Eagle's medium (C11995500BT, Gibco, China) supplemented with 10% fetal bovine serum (10100147, Gibco, Australia), 100 U/mL penicillin, and 100 U/mL streptomycin (SV30010, HyClone, China) in an atmosphere of 5% CO 2 at 37 C. The RASMCs were treated with 10 mM b-glycerophosphate (50020, Sigma-Aldrich, USA) and 1.5 mM CaCl 2 (C7250, Solarbio, China) for seven days to induce calcification [19,20]. RASMCs treated with medium without b-glycerophosphate or CaCl 2 were used as controls. ...
Objective
The pathogenesis of renal osteopathy and cardiovascular disease suggests the disordered bone–vessel axis in chronic kidney disease–mineral bone disorder (CKD–MBD). However, the mechanism of the bone–vessel axis in CKD–MBD remains unclear.
Methods
We established a CKD–MBD rat model to observe the pathophysiological phenotype of the bone–vessel axis and performed RNA sequencing of aortas to identify novel targets of the bone–vessel axis in CKD–MBD.
Results
The microarchitecture of the femoral trabecular bone deteriorated and alveolar bone loss was aggravated in CKD–MBD rats. The intact parathyroid hormone and alkaline phosphatase levels increased, 1,25-dihydroxyvitamin D3 levels decreased, and intact fibroblast growth factor-23 levels did not increase in CKD–MBD rats at 16 weeks; other bone metabolic parameters in the serum demonstrated dynamic characteristics. With calcium deposition in the abdominal aortas of CKD–MBD rats, RNA sequencing of the aortas revealed a significant decrease in inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene levels in CKD–MBD rats. A similar trend was observed in rat aortic smooth muscle cells. As a secretory protein, ITPR2 serum levels decreased at 4 weeks and slightly increased without statistical differences at 16 weeks in CKD–MBD rats. ITPR2 serum levels were significantly increased in patients with vascular calcification, negatively correlated with blood urea nitrogen levels, and positively correlated with serum tartrate-resistant acid phosphatase 5b levels.
Conclusion
These findings provide preliminary insights into the role of ITPR2 in the bone–vessel axis in CKD–MBD. Thus, ITPR2 may be a potential target of the bone–vessel axis in CKD–MBD.
... According to our previous studies [19,20], some genes are involved in VSMC phenotypic transdifferentiation. In this study, we performed long-read nanopore sequencing directly in the calcified blood vessels from CKD rats to identify potential targets for CKD-associated vascular calcification. ...
Vascular calcification is prominent in patients with chronic kidney disease (CKD) and is a strong predictor of cardiovascular mortality in the CKD population. However, the mechanism underlying CKD-associated vascular calcification remains unclear. To identify potential therapeutic targets, a 5/6 nephrectomy rat model was established by feeding of a high-phosphorous diet as the CKD group and compared with sham group rats at 4 and 16 weeks. Sequencing analyses of the rat aorta revealed 643 upregulated and 1023 downregulated genes at 4 weeks, as well as 899 upregulated and 1185 downregulated genes at 16 weeks in the CKD group compared to the sham group. Bioinformatics analyses suggested that SOST (which encodes sclerostin) and Wnt signaling are involved in CKD-associated vascular calcification. Furthermore, protein-protein interactions analysis revealed interactions between SOST, WNT5A, and WNT5B, that involved runt-related transcription factor 2 (RUNX2) and transgelin (TAGLN). SOST was increased in CKD-associated vascular calcification following reduction of the Wnt signaling, including WNT5A and WNT5B, both in vivo and in vitro. TargetScan was used to predict the microRNAs (miRNAs) targeting WNT5A and WNT5B. The expression levels of miR-542-3p, miR-298-3p, miR-376b-5p, and miR-3568 were significantly reduced, whereas that of miR-742-3p was significantly increased in calcified rat aortic vascular smooth muscle cells (VSMCs). In CKD rat aortas, the expression of miR-542-3p, miR-298-3p, miR-376b-5p, miR-3568, miR-742-3p, and miR-22-5p were significantly reduced at both 4 and 16 weeks. Altogether, owing to several assessments, potentially diagnostic and prognostic biomarkers for improving common CKD diagnostic tools were identified in this study.
Abbreviations: BUN: blood urea nitrogen; CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral bone disorder; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GO: the Gene Ontology; HE: hematoxylin-eosin; HRP: horseradish peroxidase; KEGG: Kyoto Encyclopedia of Genes and Genomes; MiRNAs: microRNAs; PAS: periodic acid-Schiff; RUNX2: runt-related transcription factor 2; SCr: serum creatinine; STRING: the Search Tool for the Retrieval of Interacting Genes/Proteins; TAGLN: transgelin; VSMC: vascular smooth muscle cell.
... Vascular calcification is a process similar to bone formation, which is highly adjustable and active 1,2 . Its occurrence is related to the phenotypic transformation from human aortic smooth muscle cells (HASMCs) to osteoblasts caused by various stimulating factors such as hyperglycemia 3,4 , oxidative stress 5 and inflammatory response 6 . ...
Objective
This work aims to screen drugs for preventing and treating vascular calcification. Method: We screened a series of 3-arylcoumarins for the detection of vascular calcification-associated factors using human aortic vascular smooth muscle cells.
Results
We found that compounds 14 and 32 significantly inhibited alkaline phosphatase (ALP) activity similar to aminoguanidine hydrochloride (AGH) in a cellular model of AGEs-induced calcification. We also found that compounds 14 and 32 could significantly decrease the levels of factors such as AGEs, intracellular calcium ions, and total ROS in the calcified cell model. Further study indicates that compound 14 could significantly inhibit the expression of P-ERK1/2, PKC, NF-κB, RAGE and OPN proteins and increased the expression of SM22-α and PPAR-γ proteins in the calcified cells.
Conclusion
We speculate that compound 14 inhibits vascular calcification by inhibiting oxidative stress and inhibiting AGEs production, suggesting that 3-arylcoumarin derivatives are potential candidates for the treatment of vascular calcification.
... The cells were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and antibiotics containing 100 U/mL of penicillin and 100 U/mL of streptomycin. To mimic calcification in RASMCs, 10 mM b-glycerophosphate was used to treat RASMCs for 72 h [27,28]. RASMCs were treated with modified Dulbecco's modified Eagle's medium without b-glycerophosphate, as a normal control. ...
... The rats were randomly assigned to two groups: the normal control group (n ¼ 7) and the CKD vascular calcification group (n ¼ 7). Rats in the CKD vascular calcification group were fed with 0.75% adenine diet (PHR1383, Sigma, USA), were injected intraperitoneally with 3 Â 10 6 U vitamin D3 (V8070, Solarbio, China), and 30 min later were given intragastrically 6.25 mg/kg nicotine (SN8140, Solarbio, China) once a day [27]. After 12 weeks of treatment, the rats were anesthetized with 1% pentobarbital sodium (11715, Sigma, USA) at 4 mL/kg to collect blood samples and aortic and renal tissue samples. ...
... RASMCs were treated with a high dose of b-glycerophosphate for 72 h and it was determined that high phosphorus could facilitate calcium deposition in RASMCs, as reported in our previous study [27]. We then performed LFQ analysis on RASMCs after high phosphorus treatment. ...
Chronic kidney disease (CKD) has recently become a serious health and social concern. Vascular calcification, a common complication of CKD, is a risk factor that increases the incidence and mortality of cardiovascular events in patients with CKD. However, there are currently no effective therapeutic targets that can facilitate treatment with fewer side effects for vascular calcification in CKD. To identify potential therapeutic targets, we performed label-free quantification (LFQ) analyses of protein samples from rat aortic vascular smooth muscle cells (RASMCs) after high-phosphorus treatment by nano-UPLC–MS/MS. We determined that ubiquitin-specific protease 47 (USP47) may be associated with CKD vascular calcification by regulating the osteogenic transdifferentiation of the vascular smooth muscle cell (VSMC) phenotype, thus suggesting a novel and potentially effective therapeutic target for CKD vascular calcification. USP47 knockdown significantly reduced the expression of β-transducin repeat-containing protein (BTRC), serine/threonine-protein kinase akt-1 (AKT1), Klotho, fibroblast growth factor (FGF23), and matrix Gla protein (MGP) in RASMCs after high-phosphorus treatment. Consistent with the results of protein–protein interaction (PPI) analyses, USP47 may be involved in regulating osteogenic transdifferentiation markers, such as runt-related transcription factor 2 (RUNX2), Klotho, FGF23, and MGP through the BTRC/AKT1 pathway upon CKD vascular calcification. These data indicate that USP47 may be associated with vascular calcification in CKD by regulating osteogenic differentiation of VSMCs. USP47 may regulate osteogenic transdifferentiation in VSMCs upon CKD vascular calcification through a process involving the BTRC/AKT1 pathway. This study identified a novel potential therapeutic target for the treatment of vascular calcification in CKD.
... Lipidomics [58][59][60][61][62][63][64]66] Association of vascular calcification with accelerated inflammation and the progression of CKD MS-based proteomics [67][68][69][70][71][72] Relationships between uremic toxins and development of vascular calcification MS-based proteomics Aptamer-based proteomics Metabolomics [69,73,74] The mechanism of inflammation and atherogenesis development in renal and non-renal conditions ...
... Nevertheless, its mech-anism remains elusive. Proteomic approaches to tackle the relationship between vascular calcification and atherosclerosis progression in CKD have been undertaken [69][70][71][72]. These studies revealed that vascular calcification is strongly connected with accelerated inflammation [70], and associated with the progression of CKD [67,68,70,105]. ...
... Both the vascular calcification and inflammation are strongly exacerbated by uremia and circulating in the blood uremic toxins, i.e., indoxyl sulfate (IS) and p-cresyl sulfate (pCS) [106][107][108]. Exposure of cells to serum uremic toxins in CKD results in morphological alterations and vascular calcification linked with CKD-related atherosclerosis [72,109]. ...
Patients with chronic kidney disease (CKD) are at increased risk of atherosclerosis and premature mortality, mainly due to cardiovascular events. However, well-known risk factors, which promote “classical” atherosclerosis are alone insufficient to explain the high prevalence of atherosclerosis-related to CKD (CKD-A). The complexity of the molecular mechanisms underlying the acceleration of CKD-A is still to be defied. To obtain a holistic picture of these changes, comprehensive proteomic approaches have been developed including global protein profiling followed by functional bioinformatics analyses of dysregulated pathways. Furthermore, proteomics surveys in combination with other “omics” techniques, i.e., transcriptomics and metabolomics as well as physiological assays provide a solid ground for interpretation of observed phenomena in the context of disease pathology. This review discusses the comprehensive application of various “omics” approaches, with emphasis on proteomics, to tackle the molecular mechanisms underlying CKD-A progression. We summarize here the recent findings derived from global proteomic approaches and underline the potential of utilizing integrative systems biology, to gain a deeper insight into the pathogenesis of CKD-A and other disorders.
... Protein concentration was determined using a BCA assay. Sample preparation was based on previous studies [57], and all samples were processed simultaneously. Samples were analyzed using LC-MS/MS. ...
... Data-dependent acquisition (DDA) was performed in the profile and positive modes with an Orbitrap analyzer under the same conditions as those used in a previous study [57]. ...
Alzheimer's disease (AD) is characterized by cognitive decline due to the accumulation of extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles in the brain, which impair glutamate (Glu) metabolism. Deproteinized Calf Blood Extractive Injection (DCBEI) is a biopharmaceutical that contains 17 types of amino acids and 5 types of nucleotides. In this study, we found that DCBEI pretreatment reduced L-Glu-dependent neuroexcitation toxicity by maintaining normal mitochondrial function in HT22 cells. DCBEI treatment also reduced the expression of pro-apoptosis proteins and increased the expression of anti-apoptosis proteins. Furthermore, DCBEI attenuated AD-like behaviors (detected via the Morris water maze test) in B6C3-Tg (APPswePSEN1dE9)/Nju double transgenic (APP/PS1) mice; this effect was associated with a reduction in the amount of Aβ and neurofibrillary tangle deposition and the concomitant reduction of phospho-Tau in the hippocampus. Metabonomic profiling revealed that DCBEI regulated the level of neurotransmitters in the hippocampus of APP/PS1 mice. Label-free proteomics revealed that DCBEI regulated the expression of Nrf-2 and its downstream targets, as well as the levels of phospho-protein kinase B and mitogen-activated protein kinase. Together, these data show that DCBEI can ameliorate AD symptoms by upregulating Nrf2-mediated antioxidative pathways and thus preventing mitochondrial apoptosis.
... Proteomics has been used to demonstrate that HG-HUVEC-Exo promotes calcification of VSMCs requiring Notch3, which regulates calcification of VSMCs through the mTOR signalling pathway [119]. Elevated levels of versican are involved in the hyperglycaemia-induced calcification/senescence by regulating the mitochondrial function of VSMCs [120], and Smarca4 is involved in high-phosphate-induced vascular calcification in a calcific rat aorta vascular smooth muscle cells [121]. Moreover, lamin A/C play a role in calcification in hyperphosphataemia [122]. ...
Vascular calcification is a high incidence and high risk disease with increasing morbidity and high mortality, which is considered the consequence of smooth muscle cell transdifferentiation initiating the mechanism of accumulation of hydroxyl calcium phosphate. Vascular calcification is also thought to be strongly associated with poor outcomes in diabetes and chronic kidney disease. Numerous studies have been accomplished; however, the specific mechanism of the disease remains unclear. Development of the genome project enhanced the understanding of life science and has entered the post-genomic era resulting in a variety of omics techniques used in studies and a large amount of available data; thus, a new perspective on data analysis has been revealed. Omics has a broader perspective and is thus advantageous over a single pathway analysis in the study of complex vascular calcification mechanisms. This paper reviews in detail various omics studies including genomics, proteomics, transcriptomics, metabolomics and multiple group studies on vascular calcification. Advances and deficiencies in the use of omics to study vascular calcification are presented in a comprehensive view. We also review the methodology of the omics studies and omics data analysis and processing. In addition, the methodology and data processing presented here can be applied to other areas. An omics landscape perspective across the boundaries between genomics, transcriptomics, proteomics and metabolomics is used to examine the mechanisms of vascular calcification. The perspective combined with various technologies also provides a direction for the subsequent exploration of clinical significance.
... Interestingly, most reports (n = 40; 60.6%) looked into the pathogenic role of non-coding RNA in VC, while histone modification (n = 6; 9.1%) [53][54][55][56][57][58], DNA methylation (n = 8; 12.1%) [5,[59][60][61][62][63][64][65], and chromatin changes (n = 3; 4.5%) [66][67][68] accounted for one-fourth only. Nine (13.6%) [69][70][71][72][73][74][75][76][77] examined the discrepancy of epigenetic signatures between subjects or animals with and without VC but not their pathogenic influences. ...
... After screening through 224 articles, we identified 66 original reports examining epigenetic processes in VC ( Figure 1). Interestingly, most reports (n = 40; 60.6%) looked into the pathogenic role of non-coding RNA in VC, while histone modification (n = 6; 9.1%) [53][54][55][56][57][58], DNA methylation (n = 8; 12.1%) [5,[59][60][61][62][63][64][65], and chromatin changes (n = 3; 4.5%) [66][67][68] accounted for one-fourth only. Nine (13.6%) [69][70][71][72][73][74][75][76][77] examined the discrepancy of epigenetic signatures between subjects or animals with and without VC but not their pathogenic influences. ...
... This is also true in human VSMCs, as shown by the decreased expression of miR-133a in calcified cells compared to non-calcified ones [28]. However, Wang et al. observed increased miR-133b expression in calcified rat aortas relative to the control [68], which was contradictory to findings of miR-133 in the non-VSMC and the VSMC experiments. This may be related to the differences in normalization controls, the status of adaptive responses, and the timing of RNA sampling during the VC process. ...
Vascular calcification (VC) is an important complication among patients of advanced age, those with chronic kidney disease, and those with diabetes mellitus. The pathophysiology of VC encompasses passive occurrence of physico-chemical calcium deposition, active cellular secretion of osteoid matrix upon exposure to metabolically noxious stimuli, or a variable combination of both processes. Epigenetic alterations have been shown to participate in this complex environment, through mechanisms including DNA methylation, non-coding RNAs, histone modifications, and chromatin changes. Despite such importance, existing reviews fail to provide a comprehensive view of all relevant reports addressing epigenetic processes in VC, and cross-talk between different epigenetic machineries is rarely examined. We conducted a systematic review based on PUBMED and MEDLINE databases up to 30 September 2019, to identify clinical, translational, and experimental reports addressing epigenetic processes in VC; we retrieved 66 original studies, among which 60.6% looked into the pathogenic role of non-coding RNA, followed by DNA methylation (12.1%), histone modification (9.1%), and chromatin changes (4.5%). Nine (13.6%) reports examined the discrepancy of epigenetic signatures between subjects or tissues with and without VC, supporting their applicability as biomarkers. Assisted by bioinformatic analyses blending in each epigenetic component, we discovered prominent interactions between microRNAs, DNA methylation, and histone modification regarding potential influences on VC risk.
