To be or not to be: endothelial cell plasticity in development, repair, and disease

Greenspan, Leah J.; Weinstein, Brant M.

doi:10.1007/s10456-020-09761-7

Cited by 23 publications

(16 citation statements)

References 168 publications

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“…After enduring cardiac injury, mice can form new coronary arteries from pre-existing endothelial cells [36,37]. The zebrafish vascular growth model is ideally suited as it mimics human vascular disease models for new drug screening and evaluation [38]. Our experimental results established that DGS can promote vascular growth in vivo by increasing the vessel length and the number of vascular outgrowths, without any effects on zebrafish development, at the effective dose.…”

Section: Discussionmentioning

confidence: 66%

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease

Zhang

Liu²,

Zong³

et al. 2022

Molecules

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Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD.

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Section: Discussionmentioning

confidence: 66%

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease

Zhang

Liu²,

Zong³

et al. 2022

Molecules

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“…Endothelial fates and states are plastic during development and in adulthood [ 215 – 217 ], resulting in heterogeneous permeability of this cell type. Neuronal activity has been proposed as a crucial modulator of influx [ 218 ] and efflux [ 219 ] transport activities in BBB vECs, thereby controlling BBB permeability dynamics [ 220 ].…”

Section: Plasticity Of Brain Endothelial Fates and States Under Physi...mentioning

confidence: 99%

Historical and current perspectives on blood endothelial cell heterogeneity in the brain

Matsuoka

Buck

Vajrala

et al. 2022

Cell. Mol. Life Sci.

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Dynamic brain activity requires timely communications between the brain parenchyma and circulating blood. Brain–blood communication is facilitated by intricate networks of brain vasculature, which display striking heterogeneity in structure and function. This vascular cell heterogeneity in the brain is fundamental to mediating diverse brain functions and has long been recognized. However, the molecular basis of this biological phenomenon has only recently begun to be elucidated. Over the past century, various animal species and in vitro systems have contributed to the accumulation of our fundamental and phylogenetic knowledge about brain vasculature, collectively advancing this research field. Historically, dye tracer and microscopic observations have provided valuable insights into the anatomical and functional properties of vasculature across the brain, and these techniques remain an important approach. Additionally, recent advances in molecular genetics and omics technologies have revealed significant molecular heterogeneity within brain endothelial and perivascular cell types. The combination of these conventional and modern approaches has enabled us to identify phenotypic differences between healthy and abnormal conditions at the single-cell level. Accordingly, our understanding of brain vascular cell states during physiological, pathological, and aging processes has rapidly expanded. In this review, we summarize major historical advances and current knowledge on blood endothelial cell heterogeneity in the brain, and discuss important unsolved questions in the field.

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“…EndMT is critical for heart valve development; endothelial cells undergo EndMT and migrate into the cardiac jelly, thereby forming endocardial cushions that will lead to formation of the valves and septa of the mature heart [ 19 ]. EndMT is driven by multiple signaling pathways, including BMP, TGF-β and Notch ( Figure 1 B) [ 20 ].…”

Section: Endothelial Plasticity and Heterogeneitymentioning

confidence: 99%

Endothelial Extracellular Vesicles: From Keepers of Health to Messengers of Disease

Mathiesen

Hamilton

Carter

et al. 2021

IJMS

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Endothelium has a rich vesicular network that allows the exchange of macromolecules between blood and parenchymal cells. This feature of endothelial cells, along with their polarized secretory machinery, makes them the second major contributor, after platelets, to the particulate secretome in circulation. Extracellular vesicles (EVs) produced by the endothelial cells mirror the remarkable molecular heterogeneity of their parent cells. Cargo molecules carried by EVs were shown to contribute to the physiological functions of endothelium and may support the plasticity and adaptation of endothelial cells in a paracrine manner. Endothelium-derived vesicles can also contribute to the pathogenesis of cardiovascular disease or can serve as prognostic or diagnostic biomarkers. Finally, endothelium-derived EVs can be used as therapeutic tools to target endothelium for drug delivery or target stromal cells via the endothelial cells. In this review we revisit the recent evidence on the heterogeneity and plasticity of endothelial cells and their EVs. We discuss the role of endothelial EVs in the maintenance of vascular homeostasis along with their contributions to endothelial adaptation and dysfunction. Finally, we evaluate the potential of endothelial EVs as disease biomarkers and their leverage as therapeutic tools.

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To be or not to be: endothelial cell plasticity in development, repair, and disease

Cited by 23 publications

References 168 publications

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease

Historical and current perspectives on blood endothelial cell heterogeneity in the brain

Endothelial Extracellular Vesicles: From Keepers of Health to Messengers of Disease

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