Characterization of Endothelial Microparticles Induced by Different Therapeutic Drugs for Infantile Hemangioma

Zhu, Junyi; Zhang, Wei; Ren, Jian‐Gang; Chen, Gang; Zhao, Yi‐Fang

doi:10.1097/fjc.0000000000000273

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…At present, the regulation of the release of microvesicles from endothelial cells by glucocorticoids is poorly characterized: A study by Thai et al [38] demonstrated that dexamethasone triggers the release of annexin A1-containing microparticles from endothelial cells, while Zhu et al [39] reported that dexamethasone inhibits the constitutive release of microparticles from human umbilical vein endothelial cells. We assume that different endothelial cell types show a different response to glucocorticoids, since the function of umbilical vein endothelial cells, a fenestrated renal endothelial cell and a very tight endothelial cell in the stem cell niche of the hippocampus, to name a few examples, have very different functions.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Neuronal Stem Cell Proliferation in the Hippocampus by Endothelial Ceramide

Gulbins¹,

Grassmé

Hoehn³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Major depressive disorder is one of the most common diseases in western countries. The disease is mainly defined by its psychiatric symptoms. However, the disease has also many symptoms outside the central nervous system, in particular cardiovascular symptoms. Recent studies demonstrated that the acid sphingomyelinase/ceramide system plays an important role in the development of major depressive disorder and functions as a target of antidepressants. Methods: Here, we investigated (i) whether ceramide accumulates in endothelial cells in the neurogenetic zone of the hippocampus after glucocorticosterone-mediated stress, (ii) whether ceramide is released into the extracellular space of the hippocampus and (iii) whether extracellular ceramide inhibits neuronal proliferation. Ceramide was determined in endothelial cell culture supernatants or extracellular hippocampus extracts by a kinase assay. Endothelial ceramide in the hippocampus was analyzed by confocal microscopy of brain sections stained with Cy3-labelled anti-ceramide antibodies and FITC-Isolectin B4. Neuronal proliferation was measured by incubation of pheochromocytoma neuronal cells with culture supernatants and extracellular hippocampus extracts. Results: Treatment of cultured endothelial cells with glucocorticosterone induces a release of ceramide into the supernatant. Likewise, treatment of mice with glucocorticosterone triggers a release of ceramide into the extracellular space of the hippocampus. The release of ceramide is inhibited by concomitant treatment with the antidepressant amitriptyline, which also inhibits the activity of the acid sphingomyelinase. Studies employing confocal microscopy revealed that ceramide is formed and accumulates exclusively in endothelial cells in the hippocampus of stressed mice, a process that was again prevented by co-application of amitriptyline. Ceramide released in the culture supernatant or into the extracellular space of the hippocampus reduced proliferation of neurons in vitro. Conclusion: The data suggest a novel model for the pathogenesis of major depressive disorder, i.e. the release of ceramide-enriched microvesicles from endothelial cells that negatively affect neuronal proliferation in the hippocampus, but may also induce cardiovascular disease and other systemic symptoms of patients with major depressive disorder.

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Section: Discussionmentioning

confidence: 99%

Regulation of Neuronal Stem Cell Proliferation in the Hippocampus by Endothelial Ceramide

Gulbins¹,

Grassmé

Hoehn³

et al. 2016

Cell Physiol Biochem

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“…As we previously described, 19 human umbilical vein endothelial cells (HUVEC) were harvested by primary culture from human umbilical cord veins. HUVEC between passage 2 and 7 were used for the experiments.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of lysyl oxidase in venous malformations: Association with vascular destabilization and sclerotherapy

Zhu

Shao

Guo

et al. 2020

The Journal of Dermatology

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Venous malformations (VM) are localized defects in vascular morphogenesis manifested by dilated venous channels with reduced perivascular cell coverage. As a vital enzyme for extracellular matrix (ECM) deposition, lysyl oxidase (LOX) plays important roles in vascular development and diseases. However, the expression and significance of LOX are unknown in VM. Herein, 22 VM specimens and eight samples of normal skin tissues were evaluated immunohistochemically for the expression of LOX, α-smooth muscle cell actin (α-SMA) and transforming growth factor-β (TGF-β). In vitro studies on human umbilical vein endothelial cells (HUVEC) were employed for determining potential mechanisms. Our results showed that LOX expression was significantly reduced in VM compared with normal skin tissues, in parallel with attenuated perivascular α-SMA + cell coverage and TGF-β downregulation in VM. Further correlation analysis indicated that LOX expression was positively correlated with perivascular α-SMA + cell coverage and TGF-β expression in VM. Moreover, marked elevation of LOX, TGF-β and α-SMA was observed in bleomycin-treated VM samples. Furthermore, our in vitro data demonstrated that both recombinant TGF-β and bleomycin induced obvious increase of LOX expression and activity and a concomitant increase in ECM components in HUVEC, which could be reversed by LOX inhibition. To our best knowledge, this study revealed for the first time the downregulation of LOX in VM and its correlation with vascular destabilization and TGF-β-induced endothelial ECM deposition. Moreover, our results highlighted that LOX may be implicated in the sclerotherapy of VM and holds promise as a therapeutic target.

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“…For miRNA detection, 250 ng of RNA was subject to cDNA synthesis and real‐time PCR using SYBR PrimeScript miRNA RT‐PCR kit (Takara, Japan). The quantitative real‐time PCR analysis was performed on a 7900HT Real‐Time PCR System (Applied Biosystems, USA) using standard conditions as we described previously (Zhu et al , ). All mRNA primers were synthesized by Sangon Biotech and were designed using PrimerBank, a validated resource for PCR primers (Wang et al , ), while miRNA‐specific primers were purchased from GeneCopoeia.…”

Section: Methodsmentioning

confidence: 99%

Characterization of microparticles in patients with venous malformations of the head and neck

et al. 2016

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Characterization of Endothelial Microparticles Induced by Different Therapeutic Drugs for Infantile Hemangioma

Cited by 11 publications

References 29 publications

Regulation of Neuronal Stem Cell Proliferation in the Hippocampus by Endothelial Ceramide

Regulation of Neuronal Stem Cell Proliferation in the Hippocampus by Endothelial Ceramide

Downregulation of lysyl oxidase in venous malformations: Association with vascular destabilization and sclerotherapy

Characterization of microparticles in patients with venous malformations of the head and neck

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