Vascular Endothelial Cell Biology: An Update

Krüger‐Genge, Anne; Blocki, Anna; Franke, R.P.; Jung, F.

doi:10.3390/ijms20184411

Cited by 711 publications

(598 citation statements)

References 150 publications

(184 reference statements)

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“…The vascular endothelium is a critical barrier maintaining homeostasis between circulating blood and surrounding tissues. It is responsible for various functions including maintaining vascular tone, preventing platelet aggregation, and regulating extravasation and angiogenesis, as well as inflammatory responses (Sabbatinelli, Vignini et al 2017, Kruger-Genge, Blocki et al 2019, ultimately regulating organ perfusion. The association of anthracycline treatment with endothelial dysfunction at the injection site has been demonstrated (Yamada, Egashira et al 2012, Sato, Kondo et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of epirubicin cause endothelial senescence while compromising metabolic activity and vascular function

Eakin

McErlain

Burke

et al. 2020

Preprint

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Anthracycline-based chemotherapy is a common treatment for cancer patients. Because it is delivered intravenously, endothelial cells are exposed first and to the highest concentrations, prior to diffusion to target cells. Not surprisingly, vascular dysfunction is a consequence of anthracycline therapy. While chemotherapy-induced endothelial damage at administration sites has been investigated, the effects of lower doses encountered by distant microvascular networks has not. The aim of this study was to investigate the impact of epirubicin, a widely used anthracycline, on healthy endothelial cells to elucidate its effects on microvascular physiology.Here, endothelial cells were briefly exposed to low doses of epirubicin to recapitulate levels in circulation following dilution in the blood and compound half-life in circulation. Both immediate and prolonged responses to treatment were assessed to determine changes in endothelial function.Epirubicin caused a decrease in proliferation and viability in hUVEC, with lower doses resulting in a senescent phenotype in a large proportion of cells, accompanied by a significant increase in proinflammatory cytokines and a significant decrease in metabolic activity. Epirubicin exposure also impaired endothelial function with delayed wound closure, reduced angiogenic potential and increased monolayer permeability downstream of VE-cadherin internalization. Primary lung endothelial cells obtained from epirubicin-treated mice similarly demonstrated reduced viability and functional impairment. In vivo, epirubicin treatment resulted in persistent reduction in lung vascular density and significantly increased infiltration of myeloid cells.Modulation of endothelial status and inflammatory tissue microenvironment observed in response to low doses of epirubicin may predict risk for long-term secondary pathologies associated with chemotherapy.3 potential for onset and success of distant metastases (Kennecke, Yerushalmi et al. 2010, Martin, Cagney et al. 2017, Xiao, Zheng et al. 2018.The aim of this study is to investigate the consequences of low-level exposure of epirubicin on healthy EC. In spite of its known reduced toxicity in comparison to Doxorubicin, this drug has not been studied in the context of its effects on microvascular physiology and the downstream impact this may have on vascular pathogenesis.In the present study, EC were exposed to short treatments of physiological doses of epirubicin, to emulate exposure in following drug dilution in the blood stream, and accounting for its relatively short half-life (Robert 1994). The aim was to investigate how EC response may educate the organ microenvironment, to what extent, and the duration and/or reversibility of EC adaptations.Human umbilical vein EC (hUVEC) were used to investigate effects on EC survival and function. Additionally, naïve (tumour-free) mice were treated with intravenous epirubicin to assess effects of treatment on lung vascular parameters, considering that lung disease and associated comorbidities are heavily assoc...

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Section: Discussionmentioning

confidence: 99%

Circulating levels of epirubicin cause endothelial senescence while compromising metabolic activity and vascular function

Eakin

McErlain

Burke

et al. 2020

Preprint

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“…These diseases affect the structure and/or function of the heart and blood vessels, and include highly prevalent disorders such as hypertension, atherosclerosis and myocardial infarction, among others [1,4,109,110]. Several metabolic risk factors involved in the development of CVD, such as hypercholesterolemia and diabetes promote EC dysfunction [4,109,111]…”

Section: Cardiovascular and Metabolic Diseasesmentioning

confidence: 99%

“…Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of low-density lipoproteins (LDL) and immune cells in the subendothelium, resulting in the formation of an atherosclerotic plaque. At early stages, morphological changes in the endothelium can be regulated by interaction with hemodynamic forces [2,3,111,119]. The distribution of blood flow in different arterial regions produces shear stress (SS): High laminar and constant (LSS) and oscillatory and low (OSS).…”

Section: Atherosclerosismentioning

confidence: 99%

“…The distribution of blood flow in different arterial regions produces shear stress (SS): High laminar and constant (LSS) and oscillatory and low (OSS). The first induces an atheroprotective phenotype in the EC, while the latter confers a pro-atherogenic phenotype [2,5,111,120,121]. The expression of atherosclerosis-related genes can be downregulated or upregulated, depending on the type of flow [120,122,123].…”

Section: Atherosclerosismentioning

confidence: 99%

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Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

et al. 2020

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Cardiovascular disease (CVD) is the leading cause of death worldwide, and extensive research has been performed to understand this disease better, using various experimental models. The endothelium plays a crucial role in the development of CVD, since it is an interface between bloodstream components, such as monocytes and platelets, and other arterial wall components. Human umbilical vein endothelial cell (HUVEC) isolation from umbilical cord was first described in 1973. To date, this model is still widely used because of the high HUVEC isolation success rate, and because HUVEC are an excellent model to study a broad array of diseases, including cardiovascular and metabolic diseases. We here review the history of HUVEC isolation, the HUVEC model over time, HUVEC culture characteristics and conditions, advantages and disadvantages of this model and finally, its applications in the area of cardiovascular diseases.

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“…The inner lining of blood vessels consists of monolayers of endothelial cells that are in direct contact with the cells and components of the blood. Consequently, these cells play a key role in vascular function, both as a barrier between the blood and the tissues and as an endocrine organ that actively regulates vascular dilation/constriction, immune responses, angiogenesis, and coagulation/fibrinolysis [8].…”

Section: Endothelial Cellsmentioning

confidence: 99%

The Vascular Involvement in Soft Tissue Fibrosis—Lessons Learned from Pathological Scarring

Huang

Ogawa

2020

IJMS

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Soft tissue fibrosis in important organs such as the heart, liver, lung, and kidney is a serious pathological process that is characterized by excessive connective tissue deposition. It is the result of chronic but progressive accumulation of fibroblasts and their production of extracellular matrix components such as collagens. Research on pathological scars, namely, hypertrophic scars and keloids, may provide important clues about the mechanisms that drive soft tissue fibrosis, in particular the vascular involvement. This is because these dermal fibrotic lesions bear all of the fibrotic characteristics seen in soft tissue fibrosis. Moreover, their location on the skin surface means they are readily observable and directly treatable and therefore more accessible to research. We will focus here on the roles that blood vessel-associated cells play in cutaneous scar pathology and assess from the literature whether these cells also contribute to other soft tissue fibroses. These cells include endothelial cells, which not only exhibit aberrant functions but also differentiate into mesenchymal cells in pathological scars. They also include pericytes, hepatic stellate cells, fibrocytes, and myofibroblasts. This article will review with broad strokes the roles that these cells play in the pathophysiology of different soft tissue fibroses. We hope that this brief but wide-ranging overview of the vascular involvement in fibrosis pathophysiology will aid research into the mechanisms underlying fibrosis and that this will eventually lead to the development of interventions that can prevent, reduce, or even reverse fibrosis formation and/or progression.

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Vascular Endothelial Cell Biology: An Update

Cited by 711 publications

References 150 publications

Circulating levels of epirubicin cause endothelial senescence while compromising metabolic activity and vascular function

Circulating levels of epirubicin cause endothelial senescence while compromising metabolic activity and vascular function

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

The Vascular Involvement in Soft Tissue Fibrosis—Lessons Learned from Pathological Scarring

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