The Pathogenesis of Atherosclerosis Based on Human Signaling Networks and Stem Cell Expression Data

Li, Wan; Huang, Hao; Li, Lei; Wang, Li; Li, Yong; Wang, Yahui; Guo, Shanshan; Li, Liansheng; Wang, Donghua; He, Yuehan; Chen, Lina

doi:10.7150/ijbs.27896

Cited by 7 publications

(7 citation statements)

References 51 publications

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“…At present, AS is one of the most common cardiovascular disorders, even though there have been significant improvements in clinical diagnosis and control of symptoms (2,7,40). AS remains a major health concern and exhibits high morbidity and mortality rates worldwide (41).…”

Section: Discussionmentioning

confidence: 99%

Baicalin inhibits proliferation and promotes apoptosis of vascular smooth muscle cells by regulating the�MEG3/p53 pathway following treatment with ox‑LDL

Liu

Min

et al. 2018

Int J Mol Med

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Atherosclerosis (AS) is a systemic disease associated with lipid metabolic disorders and abnormal proliferation of smooth muscle cells. Baicalin is a flavonoid compound isolated from the dry roots of Scutellaria baicalensis Georgi and exerts anti-proliferative effects in various types of cells. However, the effect of baicalin on AS remains unclear. In the present study, serum samples were collected from patients with AS and an in vitro model of AS was established using oxidized low-density lipoprotein (ox-LDL)-treated human aorta vascular smooth muscle cells (HA-VSMCs). The siRNA transfection and overexpression efficiency of endogenous maternally expressed gene 3 (MEG3) and the expression level of MEG3 were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of alterations in expression levels of MEG3 were assessed by MTT assay, bromodeoxyuridine incorporation assay, 5-ethynyl-2′-deoxyuridine staining, wound healing assay, immunofluorescence and western blotting in HA-VSMCs. qPCR indicated that the expression of MEG3 was reduced in serum samples from patients with AS and ox-LDL-treated HA-VSMCs, compared with serum samples from healthy patients and untreated HA-VSMCs, respectively. Further experiments indicated that ox-LDL-induced decrease of MEG3 expression was reversed by treatment with baicalin in a concentration-dependent manner. Following treatment with ox-LDL, decreased expression of MEG3 promoted proliferation and migration, and suppressed apoptosis in HA-VSMCs. Furthermore, treatment with baicalin reversed these effects on proliferation and apoptosis in ox-LDL-treated HA-VSMCs. The current study indicated that downregulated expression of MEG3 increased cell cycle-associated protein expression. However, treatment with baicalin inhibited the expression of cell-cycle associated proteins in HA-VSMCs with MEG3 knockdown. In addition, baicalin activated the p53 signaling pathway and promoted the expression and transport of p53 from the cytoplasm to nucleus following MEG3 knockdown in ox-LDL-treated HA-VSMCs. Baicalin inhibited proliferation and promoted apoptosis by regulating the expression of MEG3/p53, indicating that baicalin may serve a role in AS by activating the MEG3/p53 signaling pathway. The present study suggested a potential mechanism underlying the protective role of baicalin in the in vitro model of AS, and these results may be used to develop novel therapeutic approaches for the affected patients.

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Section: Discussionmentioning

confidence: 99%

Baicalin inhibits proliferation and promotes apoptosis of vascular smooth muscle cells by regulating the�MEG3/p53 pathway following treatment with ox‑LDL

Liu

Min

et al. 2018

Int J Mol Med

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“…and may be involved in chemotaxis of macrophages, dysregulation of related genes, dysfunction of VSMCs and other factors. 2,19,20 Research has shown that ox-LDL exerts an indispensable role in atherogenesis, and ox-LDL can interact with lectin-like ox-LDL receptor 1 (LOX-1), leading to the aberrant proliferation of VSMCs, macrophage migration and inflammatory responses. 21 Recently, numerous studies elucidated that non-coding RNAs are vital elements to regulate ox-LDL-induced dysfunction of VSMC.…”

Section: Competing Interestsmentioning

confidence: 99%

Hsa-circ_0010283 Regulates Oxidized Low-Density Lipoprotein-Induced Proliferation and Migration of Vascular Smooth Muscle Cells by Targeting the miR-133a-3p/Pregnancy-Associated Plasma Protein A Axis

Feng

Zhu

Zhang

et al. 2020

Circ J

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Background: The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the development of atherosclerosis. This study aimed to investigate the role of circular RNA-0010283 (circ_0010283) in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and the associated action mechanism. Methods and Results: The expression of circ_0010283 was investigated using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was detected by using flow cytometry assay. A transwell assay was performed to observe migration and invasion, and a scratch assay was implemented to test migration. The expression of proliferation, apoptosis and migration/invasion-related proteins was measured by using a western blot. The targeted relationship was predicted by using a bioinformatics tool (Starbase) and verified by using a dual-luciferase reporter assay, a RNA immunoprecipitation (RIP) assay and a RNA pull-down assay. circ_0010283 was highly expressed in serum samples from atherosclerosis patients and ox-LDL-treated human VSMCs (HVSMCs). circ_0010283 knockdown suppressed ox-LDL-induced proliferation, migration and invasion in HVSMCs. MicroRNA-133a-3p (miR-133a-3p) was confirmed as a target of circ_0010283, and miR-133a-3p deficiency reversed the effects of circ_0010283 knockdown. Moreover, pregnancy-associated plasma protein A (PAPPA) was targeted by miR-133a-3p, and PAPPA overexpression reversed the effects of miR-133a-3p restoration. Interestingly, circ_0010283 could regulate PAPPA expression by mediating miR-133a-3p. Conclusions: circ_0010283 participated in ox-LDL-induced dysfunctions of HVSMCs by modulating the miR-133a-3p/PAPPA pathway, suggesting that circ_0010283 might be associated with atherosclerosis pathogenesis.

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“…Thus, in this study we utilize synchrotron X-ray diffraction (SXRD) and X-ray absorption fine structure spectroscopy (XAFS) to investigate the structural changes correlated to electrochemical performance of a representative composition of nanoscale cobalt-free, lithium and manganese rich, layered MNF oxide cathode. The composition-performance trends reported in the literature to date 25,26,[29][30][31][32] are summarized in a ternary plot of experimental capacity normalized to fractional compositions of Mn, Ni and Fe in the first cycle ( Figure S2, Supplementary Material). Visualization of the composition/capacity correlations enabled us to identify and synthesize a promising composition for a Co-free, Li-rich oxide cathode, specifically Li 1.2 Mn 0.5 Ni 0.2 Fe 0.1 O 2 abbreviated below as MNF521 for detailed investigation of structural changes during cycling.…”

mentioning

confidence: 99%

Structural Studies of Capacity Activation and Reduced Voltage Fading in Li-Rich, Mn-Ni-Fe Composite Oxide Cathode

Aryal

Timofeeva

Segre

2018

J. Electrochem. Soc.

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Li-rich Mn-Ni-Fe (MNF) oxide cathodes are emerging as a low-cost alternative to commercial Ni-Mn-Co (NMC) oxides with the cost of raw iron being three orders of magnitude lower than cobalt. MNF cathodes have demonstrated potential for high capacity and high discharge voltage cathodes, however, the capacity decay and instability of discharge voltage upon cycling still need to be resolved for their successful commercialization. Both phenomena are related to the changes in structure and in this study, we utilize SXRD and XAFS to investigate the structural changes correlated to electrochemical performance of Li 1. New cathode materials with Li-rich composite layered oxides (xLi 2 MnO 3 · (1-x)LiMO 2 , where M are transition metal ions such as Mn, Ni, Co, Fe, Cr, Ti etc.) have been recently attracting significant attention because of their high experimental capacity (>250 mAhg −1 ) and high operating voltage (>3.5 V vs Li/Li + anode). [8][9][10][11][12][13] This type of cathode is formed from the structurally integrated solid solution of monoclinic Li 2 MnO 3 and rhombohedral LiMO 2 layered phases. The two crystalline phases are very similar as shown in Figure S1 (Supplementary Material) with the excess Li atoms in Li 2 MnO 3 located in the transition metal layer. The LiMO 2 phase has a theoretical capacity of 275 mAhg −1 , but is difficult to synthesize stoichiometrically 14 and its structure changes to spinel phase during long term cycling. The Li 2 MnO 3 phase has even higher theoretical capacity of 458 mAhg −1 if all the lithium could be reversibly extracted from this phase, but it is generally inactive electrochemically. It has been suggested that if the monoclinic and rhombohedral layered oxides are mixed at the nanoscale, conversion of layered LiMO 2 to spinel structure can be mitigated and the Li 2 MnO 3 phase can be activated to deliver a higher gravimetric capacity. 8,15 A possible mechanism for the improved performance of this composite material is summarized by a three component reaction including: the reversible redox reaction of the transition metal ions of rhombohedral phase at ∼4.4 V vs. Li/Li + (Eq. 1); the irreversible monoclinic Li 2 MnO 3 phase activation in the first charge at >4.6 V vs. Li/Li + (Eq. 2); and the reversible redox reaction of the converted LiMnO 2 layered phase at ∼3.3 V vs. Li/Li + (Eq. 3). [16][17][18] There is still * Electrochemical Society Student Member. * * Electrochemical Society Member.z E-mail: saryal@hawk.iit.edu disagreement on the mechanism of Li 2 MnO 3 activation and resulting contribution to the superior capacity of this Li-rich composite oxide cathode as some researchers suggest reversible oxygen reduction (O 2 2− /2O 2− ) to be the cause of improved cathode performance. 19-21LiMO 2 ⇔ Li 1−x MO 2 + xLiDespite the promise of the composite layered oxide cathodes, the challenges remaining include the decrease in capacity with cycling (capacity fading) and the decrease in positive electrode discharge potential (voltage fade). Voltage fade during battery cycling is a se...

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The Pathogenesis of Atherosclerosis Based on Human Signaling Networks and Stem Cell Expression Data

Cited by 7 publications

References 51 publications

Baicalin inhibits proliferation and promotes apoptosis of vascular smooth muscle cells by regulating the�MEG3/p53 pathway following treatment with ox‑LDL

Baicalin inhibits proliferation and promotes apoptosis of vascular smooth muscle cells by regulating the�MEG3/p53 pathway following treatment with ox‑LDL

Hsa-circ_0010283 Regulates Oxidized Low-Density Lipoprotein-Induced Proliferation and Migration of Vascular Smooth Muscle Cells by Targeting the miR-133a-3p/Pregnancy-Associated Plasma Protein A Axis

Structural Studies of Capacity Activation and Reduced Voltage Fading in Li-Rich, Mn-Ni-Fe Composite Oxide Cathode

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