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1.
Role of oxylipins generated from dietary PUFAs in the modulation of endothelial cell function.
Du, Y, Taylor, CG, Aukema, HM, Zahradka, P
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102160
Abstract
Oxylipins, which are circulating bioactive lipids generated from polyunsaturated fatty acids (PUFAs) by cyclooxygenase, lipooxygenase and cytochrome P450 enzymes, have diverse effects on endothelial cells. Although studies of the effects of oxylipins on endothelial cell function are accumulating, a review that provides a comprehensive compilation of current knowledge and recent advances in the context of vascular homeostasis is lacking. This is the first compilation of the various in vitro, ex vivo and in vivo reports to examine the effects and potential mechanisms of action of oxylipins on endothelial cells. The aggregate data indicate docosahexaenoic acid-derived oxylipins consistently show beneficial effects related to key endothelial cell functions, whereas oxylipins derived from other PUFAs exhibit both positive and negative effects. Furthermore, information is lacking for certain oxylipin classes, such as those derived from α-linolenic acid, which suggests additional studies are required to achieve a full understanding of how oxylipins affect endothelial cells.
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2.
Promising Anti-atherosclerotic Effect of Berberine: Evidence from In Vitro, In Vivo, and Clinical Studies.
Fatahian, A, Haftcheshmeh, SM, Azhdari, S, Farshchi, HK, Nikfar, B, Momtazi-Borojeni, AA
Reviews of physiology, biochemistry and pharmacology. 2020;:83-110
Abstract
Elevated levels of plasma cholesterol, impaired vascular wall, and presence of inflammatory macrophages are important atherogenic risk factors contributing to atherosclerotic plaque formation and progression. The interventions modulating these risk factors have been found to protect against atherosclerosis development and to decrease atherosclerosis-related cardiovascular disorders. Nutritional approaches involving supplements followed by improving dietary habits and lifestyle have become growingly attractive and acceptable methods used to control atherosclerosis risk factors, mainly high levels of plasma cholesterol. There are a large number of studies that show berberine, a plant bioactive compound, could ameliorate atherosclerosis-related risk factors. In the present literature review, we put together this studies and provide integrated evidence that exhibits berberine has the potential atheroprotective effect through reducing increased levels of plasma cholesterol, particularly low-density lipoprotein (LDL) cholesterol (LDL-C) via LDL receptor (LDLR)-dependent and LDL receptor-independent mechanisms, inhibiting migration and inflammatory activity of macrophages, improving the functionality of endothelial cells via anti-oxidant activities, and suppressing proliferation of vascular smooth muscle cells. In conclusion, berberine can exert inhibitory effects on the atherosclerotic plaque development mainly through LDL-lowering activity and suppressing atherogenic functions of mentioned cells. As the second achievement of this review, among the signaling pathways through which berberine regulates intracellular processes, AMP-activated protein kinase (AMPK) has a central and critical role, showing that enhancing activity of AMPK pathway can be considered as a promising therapeutic approach for atherosclerosis treatment.
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3.
Endothelial dysfunction in neuroprogressive disorders-causes and suggested treatments.
Morris, G, Puri, BK, Olive, L, Carvalho, A, Berk, M, Walder, K, Gustad, LT, Maes, M
BMC medicine. 2020;(1):305
Abstract
BACKGROUND Potential routes whereby systemic inflammation, oxidative stress and mitochondrial dysfunction may drive the development of endothelial dysfunction and atherosclerosis, even in an environment of low cholesterol, are examined. MAIN TEXT Key molecular players involved in the regulation of endothelial cell function are described, including PECAM-1, VE-cadherin, VEGFRs, SFK, Rho GEF TRIO, RAC-1, ITAM, SHP-2, MAPK/ERK, STAT-3, NF-κB, PI3K/AKT, eNOS, nitric oxide, miRNAs, KLF-4 and KLF-2. The key roles of platelet activation, xanthene oxidase and myeloperoxidase in the genesis of endothelial cell dysfunction and activation are detailed. The following roles of circulating reactive oxygen species (ROS), reactive nitrogen species and pro-inflammatory cytokines in the development of endothelial cell dysfunction are then described: paracrine signalling by circulating hydrogen peroxide, inhibition of eNOS and increased levels of mitochondrial ROS, including compromised mitochondrial dynamics, loss of calcium ion homeostasis and inactivation of SIRT-1-mediated signalling pathways. Next, loss of cellular redox homeostasis is considered, including further aspects of the roles of hydrogen peroxide signalling, the pathological consequences of elevated NF-κB, compromised S-nitrosylation and the development of hypernitrosylation and increased transcription of atherogenic miRNAs. These molecular aspects are then applied to neuroprogressive disorders by considering the following potential generators of endothelial dysfunction and activation in major depressive disorder, bipolar disorder and schizophrenia: NF-κB; platelet activation; atherogenic miRs; myeloperoxidase; xanthene oxidase and uric acid; and inflammation, oxidative stress, nitrosative stress and mitochondrial dysfunction. CONCLUSIONS Finally, on the basis of the above molecular mechanisms, details are given of potential treatment options for mitigating endothelial cell dysfunction and activation in neuroprogressive disorders.
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4.
Endothelial Progenitors in the Tumor Microenvironment.
Testa, U, Pelosi, E, Castelli, G
Advances in experimental medicine and biology. 2020;:85-115
Abstract
Tumor vascularization refers to the formation of new blood vessels within a tumor and is considered one of the hallmarks of cancer. Tumor vessels supply the tumor with oxygen and nutrients, required to sustain tumor growth and progression, and provide a gateway for tumor metastasis through the blood or lymphatic vasculature. Blood vessels display an angiocrine capacity of supporting the survival and proliferation of tumor cells through the production of growth factors and cytokines. Although tumor vasculature plays an essential role in sustaining tumor growth, it represents at the same time an essential way to deliver drugs and immune cells to the tumor. However, tumor vasculature exhibits many morphological and functional abnormalities, thus resulting in the formation of hypoxic areas within tumors, believed to represent a mechanism to maintain tumor cells in an invasive state.Tumors are vascularized through a variety of modalities, mainly represented by angiogenesis, where VEGF and other members of the VEGF family play a key role. This has represented the basis for the development of anti-VEGF blocking agents and their use in cancer therapy: however, these agents failed to induce significant therapeutic effects.Much less is known about the cellular origin of vessel network in tumors. Various cell types may contribute to tumor vasculature in different tumors or in the same tumor, such as mature endothelial cells, endothelial progenitor cells (EPCs), or the same tumor cells through a process of transdifferentiation. Early studies have suggested a role for bone marrow-derived EPCs; these cells do not are true EPCs but myeloid progenitors differentiating into monocytic cells, exerting a proangiogenic effect through a paracrine mechanism. More recent studies have shown the existence of tissue-resident endothelial vascular progenitors (EVPs) present at the level of vessel endothelium and their possible involvement as cells of origin of tumor vasculature.
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5.
Signalling, Metabolic Pathways and Iron Homeostasis in Endothelial Cells in Health, Atherosclerosis and Alzheimer's Disease.
Bosseboeuf, E, Raimondi, C
Cells. 2020;(9)
Abstract
Endothelial cells drive the formation of new blood vessels in physiological and pathological contexts such as embryonic development, wound healing, cancer and ocular diseases. Once formed, all vessels of the vasculature system present an endothelial monolayer (the endothelium), lining the luminal wall of the vessels, that regulates gas and nutrient exchange between the circulating blood and tissues, contributing to maintaining tissue and vascular homeostasis. To perform their functions, endothelial cells integrate signalling pathways promoted by growth factors, cytokines, extracellular matrix components and signals from mechanosensory complexes sensing the blood flow. New evidence shows that endothelial cells rely on specific metabolic pathways for distinct cellular functions and that the integration of signalling and metabolic pathways regulates endothelial-dependent processes such as angiogenesis and vascular homeostasis. In this review, we provide an overview of endothelial functions and the recent advances in understanding the role of endothelial signalling and metabolism in physiological processes such as angiogenesis and vascular homeostasis and vascular diseases. Also, we focus on the signalling pathways promoted by the transmembrane protein Neuropilin-1 (NRP1) in endothelial cells, its recently discovered role in regulating mitochondrial function and iron homeostasis and the role of mitochondrial dysfunction and iron in atherosclerosis and neurodegenerative diseases.
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6.
Endothelial Cells in the Tumor Microenvironment.
Sobierajska, K, Ciszewski, WM, Sacewicz-Hofman, I, Niewiarowska, J
Advances in experimental medicine and biology. 2020;:71-86
Abstract
Angiogenesis is a critical process required for tumor progression. Newly formed blood vessels provide nutrition and oxygen to the tumor contributing to its growth and development. However, endothelium also plays other functions that promote tumor metastasis. It is involved in intravasation, which allows invasive cancer cells to translocate into the blood vessel lumen. This phenomenon is an important stage for cancer metastasis. Besides direct association with cancer development, endothelial cells are one of the main sources of cancer-associated fibroblasts (CAFs). The heterogeneous group of CAFs is the main inductor of migration and invasion abilities of cancer cells. Therefore, the endothelium is also indirectly responsible for metastasis. Considering the above, the endothelium is one of the important targets of anticancer therapy. In the chapter, we will present mechanisms regulating endothelial function, dependent on cancer and cancer niche cells. We will focus on possibilities of suppressing pro-metastatic endothelial functions, applied in anti-cancer therapies.
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7.
Protective Effects of Polyphenols Present in Mediterranean Diet on Endothelial Dysfunction.
Stromsnes, K, Mas-Bargues, C, Gambini, J, Gimeno-Mallench, L
Oxidative medicine and cellular longevity. 2020;:2097096
Abstract
Endothelial dysfunction tends to be the initial indicator in proinflammatory state and macro- and microvascular complications, such as atherosclerosis and cardiovascular diseases. It has been shown that certain compounds in diet can generate beneficial effects on cardiovascular disease due to its interactions with endothelial cells. Thus, this review is aimed at investigating whether certain polyphenols present in the Mediterranean diet, specifically catechin, quercetin, resveratrol, and urolithin, could exert positive effects on endothelial dysfunction. After analysis of numerous papers, we found that polyphenols aiding endothelial function is beneficial not only for patients with cardiovascular disease, diabetes, or endothelial dysfunction but for all people as it can improve the effects of aging on the endothelia. The additional benefit of these polyphenols on weight loss further improves health and lowers the risk of several diseases, including those caused by endothelial dysfunction. However, it is important to note that the dosages in the majorities of the studies mentioned in this review were of supplemental rather than nutritionally relevant quantities, and therefore, the recommended dosages are difficult to determine.
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8.
Bioengineering human vascular networks: trends and directions in endothelial and perivascular cell sources.
Wang, K, Lin, RZ, Melero-Martin, JM
Cellular and molecular life sciences : CMLS. 2019;(3):421-439
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Abstract
Tissue engineering holds great promise in regenerative medicine. However, the field of tissue engineering faces a myriad of difficulties. A major challenge is the necessity to integrate vascular networks into bioengineered constructs to enable physiological functions including adequate oxygenation, nutrient delivery, and removal of waste products. The last two decades have seen remarkable progress in our collective effort to bioengineer human-specific vascular networks. Studies have included both in vitro and in vivo investigations, and multiple methodologies have found varying degrees of success. What most approaches to bioengineer human vascular networks have in common, however, is the synergistic use of both (1) endothelial cells (ECs)-the cells used to line the lumen of the vascular structures and (2) perivascular cells-usually used to support EC function and provide perivascular stability to the networks. Here, we have highlighted trends in the use of various cellular sources over the last two decades of vascular network bioengineering research. To this end, we comprehensively reviewed all life science and biomedical publications available at the MEDLINE database up to 2018. Emphasis was put on selective studies that definitively used human ECs and were specifically related to bioengineering vascular networks. To facilitate this analysis, all papers were stratified by publication year and then analyzed according to their use of EC and perivascular cell types. This study provides an illustrating discussion on how each alternative source of cells has come to be used in the field. Our intention was to reveal trends and to provide new insights into the trajectory of vascular network bioengineering with regard to cellular sources.
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9.
Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling.
Thakore, P, Earley, S
Comprehensive Physiology. 2019;(3):1249-1277
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Abstract
The vascular endothelium is a broadly distributed and highly specialized organ. The endothelium has a number of functions including the control of blood vessels diameter through the production and release of potent vasoactive substances or direct electrical communication with underlying smooth muscle cells, regulates the permeability of the vascular barrier, stimulates the formation of new blood vessels, and influences inflammatory and thrombotic processes. Endothelial cells that make up the endothelium express a variety of cell-surface receptors and ion channels on the plasma membrane that are capable of detecting circulating hormones, neurotransmitters, oxygen tension, and shear stress across the vascular wall. Changes in these stimuli activate signaling cascades that initiate an appropriate physiological response. Increases in the global intracellular Ca2+ concentration and localized Ca2+ signals that occur within specialized subcellular microdomains are fundamentally important components of many signaling pathways in the endothelium. The transient receptor potential (TRP) channels are a superfamily of cation-permeable ion channels that act as a primary means of increasing cytosolic Ca2+ in endothelial cells. Consequently, TRP channels are vitally important for the major functions of the endothelium. In this review, we provide an in-depth discussion of Ca2+ -permeable TRP channels in the endothelium and their role in vascular regulation. © 2019 American Physiological Society. Compr Physiol 9:1249-1277, 2019.
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Triglycerides and endothelial function: molecular biology to clinical perspective.
Kajikawa, M, Higashi, Y
Current opinion in lipidology. 2019;(5):364-369
Abstract
PURPOSE OF REVIEW Recently, a high level of triglycerides has attracted much attention as an important residual risk factor of cardiovascular events. We will review and show the mechanisms underlying the association of endothelial dysfunction with hypertriglyceridemia and present clinical evidence for a relationship between endothelial function and triglycerides. RECENT FINDINGS Clinical studies have shown that hypertriglyceridemia is associated with endothelial dysfunction. It is likely that hypertriglyceridemia impairs endothelial function through direct and indirect mechanisms. Therefore, hypertriglyceridemia is recognized as a therapeutic target in the treatment of endothelial dysfunction. Although experimental and clinical studies have shown that fibrates and omega-3 fatty acids not only decrease triglycerides but also improve endothelial function, the effects of these therapies on cardiovascular events are controversial. SUMMARY Accumulating evidence suggests that hypertriglyceridemia is an independent risk factor for endothelial dysfunction. Triglycerides should be considered more seriously as a future target to reduce cardiovascular events. Results of ongoing studies may show the benefit of lowering triglycerides and provide new standards of care for patients with hypertriglyceridemia possibly through improvement in endothelial function.