Ameliorative effect of allicin on vascular calcification via inhibiting endoplasmic reticulum stress

Wang, Qin; Lin, Ping; Li, Feng; Ren, Qian; Xie, Xiaofeng; Zhang, Bin

doi:10.1177/17085381211035291

Cited by 4 publications

(4 citation statements)

References 52 publications

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“…We found that overexpression of DBP in CKD rats led to a reduction in the expression of RUNX2 and BMP2. Both RUNX2 and BMP2 serve as indicators of the osteoblastic phenotype in VSMCs and are often highly expressed in calcified aortas [ 27 ]. Therefore, the reduced levels of RUNX2 and BMP2 suggested a reduction in VC.…”

Section: Discussionmentioning

confidence: 99%

D-box-binding protein alleviates vascular calcification in rats with chronic kidney disease by activating microRNA-195-5p and downregulating cyclin D1

Yao,

Zhao,

Zhang

et al. 2024

Biomol Biomed

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Vascular calcification (VC) is a critical complication in chronic kidney disease (CKD), where transcription factors (TFs) and microRNAs (miRs) could potentially play a pivotal role in its pathogenesis and progression. To explore the potential molecular mechanism by which the TF D-box-binding protein (DBP) regulates the miR-195-5p/cyclin D1 (CCND1) axis and its impact on aortic VC in CKD rats, we established a rat model of CKD with VC through a 5/6 nephrectomy procedure. This model was treated with lentivirus overexpressing DBP or CCND1 to analyze their roles in aortic VC. Additionally, an in vitro cell model of VC was induced by high phosphorus. This model underwent transfection with lentivirus overexpressing DBP or miR-195-5p mimic/inhibitor to confirm their regulatory roles in aortic VC in vitro. We assessed the interactions between DBP and miR-195-5p, as well as between miR-195-5p and CCND1. Our results indicated that the expression of DBP and miR-195-5p was reduced, while CCND1 levels were elevated in both the rat and cell models. Overexpression of miR-195-5p inhibited VC in vascular smooth muscle cells (VSMCs). Bioinformatics prediction and dual luciferase assays confirmed that DBP could act as a TF to enhance miR-195-5p expression, with Ccnd1 identified as a downstream target gene of miR-195-5p. Overexpression of DBP inhibited aortic calcification in CKD rats, whereas overexpression of CCND1 produced the opposite effect. In conclusion, the TF DBP can inhibit CCND1 expression through transcriptional activation of miR-195-5p, thereby preventing VC in rats with CKD.

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Section: Discussionmentioning

confidence: 99%

D-box-binding protein alleviates vascular calcification in rats with chronic kidney disease by activating microRNA-195-5p and downregulating cyclin D1

Yao,

Zhao,

Zhang

et al. 2024

Biomol Biomed

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“…Intriguingly, induced ATF4 expression due to increased stearate could contribute to enhanced osteoblastic differentiation as well as mineralization of VSMCs, involved with the activated PERK‐eIF2α pathway, thereby augmenting vascular calcification (Masuda et al 2012). Inhibition of PERK/eIF2α/ATF4 cascades due to Allicin treatment can attenuate aortic vascular calcification and stiffness (Wang et al 2022). Furthermore, inactivated PERK‐eIF2α‐ATF4 pathway due to pre‐culture of VSMCs using terpinen‐4‐ol or a SIRT1 agonist ameliorates vascular calcification (Zhang et al 2021a, b).…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-129 and miR-342 derived from intermittent hypoxia-stimulated vascular smooth muscle cells inhibit the eIF2α/ATF4 axis from preventing calcified aortic valvular disease

Huang,

Han,

Yang

et al. 2023

J. Cell Commun. Signal.

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This study aims to elucidate the role of miR-129/miR-342 loaded in exosomes derived from vascular smooth muscle cells (VSMCs) stimulated by intermittent hypoxia in calcified aortic valvular disease (CAVD). Bioinformatics analysis was conducted to identify differentially expressed miRs in VSMCs-derived exosomes and CAVD samples, and their potential target genes were predicted. VSMCs were exposed to intermittent hypoxia to induce stimulation, followed by isolation of exosomes. Valvular interstitial cells (VICs) were cultured in vitro to investigate the impact of miR-129/miR-342 on VICs' osteogenic differentiation and aortic valve calcification with eIF2α. A CAVD mouse model was established using ApoE knockout mice for in vivo validation. In CAVD samples, miR-129 and miR-342 were downregulated, while eIF2α and ATF4 were upregulated. miR-129 and miR-342 exhibited inhibitory effects on eIF2α through targeted regulation. Exosomes released from intermittently hypoxia-stimulated VSMCs contained miR-129 and miR-342. Overexpression of miR-129 and miR-342, or silencing ATF4, suppressed VICs' osteogenic differentiation and aortic valve calcification, which could be rescued by overexpressed eIF2α. Collectively, intermittent hypoxia stimulation of VSMCs leads to the secretion of exosomes that activate the miR-129/miR-342 dual pathway, thereby inhibiting the eIF2α/ATF4 axis and attenuating VICs' osteogenic differentiation and CAVD progression.

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“…As all three branches of the UPR, the protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase and endonuclease-1α (IRE1α), and activating transcription factor (ATF), are activated during bone formation to regulate expression of osteogenic genes, it is crucial to elucidate the role of endoplasmin in valve calcification [42][43][44][45][46]. Importantly, elevated levels of endoplasmin have been found in calcified vascular smooth muscle cells [47] and in the calcified aorta [48,49], consistent with our results.…”

Section: Discussionmentioning

confidence: 99%

Prioritization of Candidate Biomarkers for Degenerative Aortic Stenosis through a Systems Biology-Based In-Silico Approach

Corbacho-Alonso

Sastre-Oliva

Corros

et al. 2022

JPM

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Degenerative aortic stenosis is the most common valve disease in the elderly and is usually confirmed at an advanced stage when the only treatment is surgery. This work is focused on the study of previously defined biomarkers through systems biology and artificial neuronal networks to understand their potential role within aortic stenosis. The goal was generating a molecular panel of biomarkers to ensure an accurate diagnosis, risk stratification, and follow-up of aortic stenosis patients. We used in silico studies to combine and re-analyze the results of our previous studies and, with information from multiple databases, established a mathematical model. After this, we prioritized two proteins related to endoplasmic reticulum stress, thrombospondin-1 and endoplasmin, which have not been previously validated as markers for aortic stenosis, and analyzed them in a cell model and in plasma from human subjects. Large-scale bioinformatics tools allow us to extract the most significant results after using high throughput analytical techniques. Our results could help to prevent the development of aortic stenosis and open the possibility of a future strategy based on more specific therapies.

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Ameliorative effect of allicin on vascular calcification via inhibiting endoplasmic reticulum stress

Cited by 4 publications

References 52 publications

D-box-binding protein alleviates vascular calcification in rats with chronic kidney disease by activating microRNA-195-5p and downregulating cyclin D1

D-box-binding protein alleviates vascular calcification in rats with chronic kidney disease by activating microRNA-195-5p and downregulating cyclin D1

Exosomal miR-129 and miR-342 derived from intermittent hypoxia-stimulated vascular smooth muscle cells inhibit the eIF2α/ATF4 axis from preventing calcified aortic valvular disease

Prioritization of Candidate Biomarkers for Degenerative Aortic Stenosis through a Systems Biology-Based In-Silico Approach

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