Herpud1 deficiency could reduce amyloid-β40 expression and thereby suppress homocysteine-induced atherosclerosis by blocking the JNK/AP1 pathway

Gao, Feidan; Zhang, Jie; Ni, Tingjuan; Lin, Na; Lin, Hui; Luo, Hongwei; Guo, Hangyuan

doi:10.1007/s13105-020-00741-5

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…AP-1, a transcription factor, participates in the regulation of proliferation, migration and cell cycle progression in VSMCs 42 - 44 . Additionally, the activation of AP-1 plays an important role in the process of aging 45 , atherosclerosis 46 , 47 , and vascular remodeling 48 - 50 . According to the latest research, AP-1 plays an essential role in the cardiomyocyte response to injury by regulating chromatin accessibility changes, thereby allowing the activation of gene expression programs that promote cardiomyocyte dedifferentiation, proliferation, and protrusion into the injured area 51 .…”

Section: Discussionmentioning

confidence: 99%

M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation

Yan¹,

Li²,

Yin³

et al. 2020

Theranostics

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Rationale: For intravascular stent implantation to be successful, the processes of vascular tissue repair and therapy are considered to be critical. However, the mechanisms underlying the eventual fate of vascular smooth muscle cells (VSMCs) during vascular tissue repair remains elusive. In this study, we hypothesized that M2 macrophage-derived exosomes to mediate cell-to-cell crosstalk and induce dedifferentiation phenotypes in VSMCs. Methods: In vivo , 316L bare metal stents (BMS) were implanted from the left iliac artery into the abdominal aorta of 12-week-old male Sprague-Dawley (SD) rats for 7 and 28 days. Hematoxylin and eosin (HE) were used to stain the neointimal lesions. En-face immunofluorescence staining of smooth muscle 22 alpha (SM22α) and CD68 showed the rat aorta smooth muscle cells (RASMCs) and macrophages. Immunohistochemical staining of total galactose-specific lectin 3 (MAC-2) and total chitinase 3-like 3 (YM-1) showed the total macrophages and M2 macrophages. In vitro , exosomes derived from IL-4+IL-13-treated macrophages (M2Es) were isolated by ultracentrifugation and characterized based on their specific morphology. Ki-67 staining was conducted to assess the effects of the M2Es on the proliferation of RASMCs. An atomic force microscope (AFM) was used to detect the stiffness of the VSMCs. GW4869 was used to inhibit exosome release. RNA-seq was performed to determine the mRNA profiles of the RASMCs and M2Es-treated RASMCs. Quantitative real-time PCR (qRT-PCR) analysis was conducted to detect the expression levels of the mRNAs. Western blotting was used to detect the candidate protein expression levels. T-5224 was used to inhibit the DNA binding activity of AP-1 in RASMCs. Results: M2Es promote c-KIT expression and softening of nearby VSMCs, hence accelerating the vascular tissue repair process. VSMCs co-cultured in vitro with M2 macrophages presented an increased capacity for de-differentiation and softening, which was exosome dependent. In addition, the isolated M2Es helped to promote VSMC dedifferentiation and softening. Furthermore, the M2Es enhanced vascular tissue repair potency by upregulation of VSMCs c-KIT expression via activation of the c-Jun/activator protein 1 (AP-1) signaling pathway . Conclusions: The findings of this study emphasize the prominent role of M2Es during VSMC dedifferentiation and vascular tissue repair via activation of the c-Jun/AP-1 signaling pathway, which has a profound impact on the therapeutic strategies of coronary stenting techniques.

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Section: Discussionmentioning

confidence: 99%

M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation

Yan¹,

Li²,

Yin³

et al. 2020

Theranostics

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“…Many animal and cell studies have shown that Aβ 1−40 is involved in the formation of atherosclerosis through various channels. Knockout of Herpud1 reduced Aβ 1−40 expression other than lipid metabolism and alleviated atherosclerosis via JNK/AP1 signaling inhibition [ 26 ]. Neuronal overexpression of Aβ in atherosclerotic mice predisposes to macrophage activation and endothelial dysfunction, which promotes atherosclerosis [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Atherosclerosis is associated with plasma Aβ levels in non-hypertension patients

Chen,

Anqi,

Ling

et al. 2024

BMC Neurol

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Background Growing evidence indicated that to develop of atherosclerosis observed more often by people with Alzheimer’s disease (AD), but the underlying mechanism is not fully clarified. Considering that amyloid-β (Aβ) deposition in the brain is the key pathophysiology of AD and plasma Aβ is closely relate to Aβ deposition in the brain, in the present study, we investigated the relationships between atherosclerosis and plasma Aβ levels. Methods This was a population based cross-sectional study. Patients with high risk of atherosclerosis from Qubao Village, Xi’an were underwent carotid ultrasound for assessment of atherosclerosis. Venous blood was collected on empty stomach in the morning and plasma Aβ1−40 and Aβ1−42 levels were measured using ELISA. Multivariate logistic regression analysis was performed to investigate the relationships between carotid atherosclerosis (CAS) and plasma Aβ levels. Results Among 344 patients with high risk of atherosclerosis, 251(73.0%) had CAS. In the univariate analysis, the plasma Aβ levels had no significant differences between CAS group and non-CAS group (Aβ1−40: 53.07 ± 9.24 pg/ml vs. 51.67 ± 9.11pg/ml, p = 0.211; Aβ1−42: 40.10 ± 5.57 pg/ml vs. 40.70 pg/ml ± 6.37pg/ml, p = 0.285). Multivariate logistic analysis showed that plasma Aβ levels were not associated with CAS (Aβ1−40: OR = 1.019, 95%CI: 0.985–1.054, p = 0.270;Aβ1−42: OR = 1.028, 95%CI: 0.980–1.079, p = 0.256) in the total study population. After stratified by hypertension, CAS was associated with plasma Aβ1−40 positively (OR = 1.063, 95%CI: 1.007–1.122, p = 0.028) in the non-hypertension group, but not in hypertensive group. When the plasma Aβ concentrations were classified into four groups according to its quartile, the highest level of plasma Aβ1−40 group was associated with CAS significantly (OR = 4.465, 95%CI: 1.024–19.474, p = 0.046). Conclusion Among patients with high risk of atherosclerosis, CAS was associated with higher plasma Aβ1−40 level in non-hypertension group, but not in hypertension group. These indicated that atherosclerosis is associated with plasma Aβ level, but the relationship may be confounded by hypertension.

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“…Accumulating evidence has confirmed that pathological serum level of homocysteine (Hcy) is closely related to the increased frequency of cardiovascular disease. 1 Hyperhomocysteinemia (HHcy) is likely related to the enhanced production of proinflammatory cytokines. 2 Recent notions indicate that macrophages derived from monocytes are key cells in the inflammatory process.…”

Section: Introductionmentioning

confidence: 99%

TGFB3-AS1 promotes Hcy-induced inflammation of macrophages via inhibiting the maturity of miR-144 and upregulating Rap1a

Zhang

Hao

et al. 2021

Molecular Therapy - Nucleic Acids

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Herpud1 deficiency could reduce amyloid-β40 expression and thereby suppress homocysteine-induced atherosclerosis by blocking the JNK/AP1 pathway

Cited by 6 publications

References 38 publications

M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation

M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation

Atherosclerosis is associated with plasma Aβ levels in non-hypertension patients

TGFB3-AS1 promotes Hcy-induced inflammation of macrophages via inhibiting the maturity of miR-144 and upregulating Rap1a

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