Roles and mechanisms of MFG-E8 in vascular aging-related diseases

Ni, Yu‐Qing; Zhan, Jicheng; Liu, You‐Shuo

doi:10.1016/j.arr.2020.101176

Cited by 35 publications

(31 citation statements)

References 108 publications

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“…In contrast, because adiponectin and leptin are adipokines closely linked to lipid metabolism, these markers had a lower correlation with glucose level [ 8 ], which is the major component of metabolic syndrome. MFG-E8 also had a significant association with pulse wave velocity in this study, which is in accordance with the results of previous studies, suggesting that MFG-E8 could be a promising diagnostic biomarker in vascular disease [ 19 - 22 ]. It is suggested that MFG-E8 cause an age-associated increase in extracellular matrix adhesion molecules.…”

Section: Discussionsupporting

confidence: 93%

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome

et al. 2021

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Total number of figures and tables 3 figures and 3 tables List of Abbreviations HDL, high density lipoprotein; MFG-E8, milk fat globule-EGF factor-8; S-MAS, Seoul Metabolic Syndrome; BP, blood pressure; AUROC, area under the receiver operating characteristic curve; CI, confidence interval; OR, odds ratio; HR, hazard ratio; BMI, body mass index; LDL, low density lipoprotein; hsCRP, high sensitivity C-reactive protein.

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Section: Discussionsupporting

confidence: 93%

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome

et al. 2021

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“…MFG-E8 deficiency substantially alleviates Ang II induced adverse arterial remodeling including IMT, collagen deposition and elastic fiber breakdown in KO vs WT, which have hypertension. Increases in arterial MMP-2 activation, TGF-β fibrotic signaling, inflammation, proliferation of VSMCs in mice are the molecular and cellular mechanisms of arterial elastic network collapse, collagen deposition, and IMT 2,7-10,12,13,18,20,29,38…”

Section: Discussionmentioning

confidence: 99%

“…Milk fat globule-epidermal growth factor 8 (MFG-E8) is a secreted glycoprotein enriched in the milk fat globule that was initially discovered as a bridging molecule between apoptotic cells and macrophages for the clearance of cellular debris, known as efferocytosis 5,6 . It is also known to be involved in inflammatory vascular conditions 7-13 . Prior in vivo studies have demonstrated that the MFG-E8 protein increases during arterial aging and arterial injury, and in hypertensive, diabetic, and atherosclerotic arterial walls 7-12,14 .…”

Section: Introductionmentioning

confidence: 99%

The Inflammatory Role of Milk Fat Globule Epidermal Growth Factor VIII in Angiotensin II Induced Arterial Remodeling

Liu²,

Zhu³

et al. 2021

Preprint

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Angiotensin II (Ang II) and milk fat globule-epidermal growth factor VIII (MFG-E8) are increased in the aged arterial wall and are involved in remodeling. However, the precise interactions between Ang II and MFG-E8 in proinflammatory arterial remodeling remains unknown. In this study, both MFG-E8 knock out (KO) and wild-type (WT) mice were infused with Ang II via an osmotic mini-pump. After infusion with Ang II, increases in systolic blood pressure (SBP) and circulating Ang II were observed in all animals, but changes to the aortic molecular, cellular, and structural remodeling were dependent on genotype (presence or absence of MFG-E8) (p<0.05, two-way ANOVA): (1) Ang II infusion substantially increased intimal-medial thickness, elastic lamina degradation, collagen deposition, and proliferation of vascular smooth muscle cells (VSMCs) in the aortic walls in WT; in contrast, in MFG-E8 KO mice, these cellular and matrix effects were significantly reduced; (2) Ang II treatment significant increased the activation and expression of matrix metallopeptidase type 2 (MMP-2), activated transforming growth factor-beta 1 (TGF-β1) and its downstream signaling molecule phosphorylation mothers against decapentaplegic homolog 2 (p-Smad2), and collagen type I production in the aortic walls of WT mice, however, in KO mice, these molecular effects were significantly reduced; (3) Ang II treatment increased nuclear factor-kappa beta (NF-κB) p65, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha 1 (TNF-α) protein expression by at least two fold in the aortic walls of WT mice, conversely, in MFG-E8 KO mice, no significant proinflammatory changes were found. Taken together, these findings suggest that Ang II effects on proinflammatory arterial remodeling are MFG-E8 genotype -dependent.

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“…Although recent studies have found that MFGE8 is related to aging, there are only a few reports on its relationship with VSMCs. Recently, we first demonstrated the roles and mechanisms of MFGE8 in vascular aging-related diseases with special emphasis on the functions of ECs and VSMCs (Ni et al, 2020b). However, the association between MFGE8 and diabetic vascular calcification/aging has not been reported to date.…”

Section: Discussionmentioning

confidence: 99%

Exosomal MFGE8 from high glucose induced endothelial cells is involved in calcification/senescence of vascular smooth muscle cells

Lin

et al. 2021

Preprint

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Vascular calcification/aging is a crucial feature of diabetic macro vasculopathy, resulting in serious cardiovascular diseases. The calcification/senescence of vascular smooth muscle cells (VSMCs) induced by hyperglycemia can cause diabetic vascular calcification/aging. However, the mechanism of VSMCs calcification/senescence involved in diabetic vascular calcification/aging remains unknown. The purpose of this study was to determine how the high glucose (HG) information in circulating blood is transmitted from vascular endothelial cells (ECs) to VSMCs, which are not contacted with blood directly. Exosomes have attracted much attention for their vital roles in regulating cell-to-cell communication. In this study, we found that milk fat globule epidermal growth factor 8 (MFGE8) was enriched in high glucose induced human umbilical vein endothelial cell exosomes (HG-HUVEC-Exo) and regulate VSMCs calcification/senescence, characterized by up-regulated expressions of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as the increased mineralized nodules and senescence-associated β-galactosidase (SA-β-gal) positive cells. Upstream mechanism studies showed that sirtuin1 (SIRT1) was involved in VSMCs calcification/senescence by affecting the expression of MFGE8. We also found that inflammatory response mediated by IL-1β, IL-6, and IL-8 was closely associated with MFGE8 and played a key role in regulating HG-HUVEC-Exo-induced VSMCs calcification/senescence. These findings provide a new insight into the mechanism of exosomal MFGE8 as a potential preventive and therapeutic target for the intervention of diabetic vascular calcification/aging.

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Roles and mechanisms of MFG-E8 in vascular aging-related diseases

Cited by 35 publications

References 108 publications

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome

The Inflammatory Role of Milk Fat Globule Epidermal Growth Factor VIII in Angiotensin II Induced Arterial Remodeling

Exosomal MFGE8 from high glucose induced endothelial cells is involved in calcification/senescence of vascular smooth muscle cells

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