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Critical Care Clinics Apr 2020Guided by organ-specific signals in both development and disease response, the heterogeneous endothelial cell population is a dynamic member of the vasculature.... (Review)
Review
Guided by organ-specific signals in both development and disease response, the heterogeneous endothelial cell population is a dynamic member of the vasculature. Functioning as the gatekeeper to fluid, inflammatory cells, oxygen, and nutrients, endothelial cell communication with its local environment is critical. Impairment of endothelial cell-cell communication not only disrupts this signaling process, but also contributes to pathologic disease progression. Expanding our understanding of those processes that mediate endothelial cell-cell communication is an important step in the approach to treatment of disease processes.
Topics: Cell Communication; Cell Differentiation; Disease Progression; Endothelium; Endothelium, Vascular; Homeostasis; Humans
PubMed: 32172808
DOI: 10.1016/j.ccc.2019.11.001 -
Reviews in Endocrine & Metabolic... Mar 2013
Review
Topics: Animals; Diabetes Mellitus; Endothelium, Vascular; Humans; Insulin Resistance; Models, Biological
PubMed: 23397463
DOI: 10.1007/s11154-013-9238-8 -
Molecules (Basel, Switzerland) Nov 2019Cardiovascular functionality strictly depends on endothelial cell trophism and proper biochemical function. Any condition (environmental, pharmacological/toxicological,... (Review)
Review
Cardiovascular functionality strictly depends on endothelial cell trophism and proper biochemical function. Any condition (environmental, pharmacological/toxicological, physical, or neuro-humoral) that changes the vascular endothelium has great consequences for the organism's wellness and on the outcome and evolution of severe cardiovascular pathologies. Thus, knowledge of the mechanisms, both endogenous and external, that affect endothelial dysfunction is pivotal to preventing and treating these disorders. In recent decades, significant attention has been focused on gut microbiota and how these symbiotic microorganisms can influence host health and disease development. Indeed, dysbiosis has been reported to be at the base of a range of different pathologies, including pathologies of the cardiovascular system. The study of the mechanism underlying this relationship has led to the identification of a series of metabolites (released by gut bacteria) that exert different effects on all the components of the vascular system, and in particular on endothelial cells. The imbalance of factors promoting or blunting endothelial cell viability and function and angiogenesis seems to be a potential target for the development of new therapeutic interventions. This review highlights the circulating factors identified to date, either directly produced by gut microbes or resulting from the metabolism of diet derivatives as polyphenols.
Topics: Animals; Cardiovascular Diseases; Cell Survival; Endothelial Cells; Endothelium, Vascular; Gastrointestinal Microbiome; Humans
PubMed: 31694161
DOI: 10.3390/molecules24213992 -
Critical Care (London, England) Jun 2020In severe SARS-CoV-2 infections, emerging data including recent histopathological studies have emphasized the crucial role of endothelial cells (ECs) in vascular... (Review)
Review
In severe SARS-CoV-2 infections, emerging data including recent histopathological studies have emphasized the crucial role of endothelial cells (ECs) in vascular dysfunction, immunothrombosis, and inflammation.Histopathological studies have evidenced direct viral infection of ECs, endotheliitis with diffuse endothelial inflammation, and micro- and macrovascular thrombosis both in the venous and arterial circulations. Venous thrombotic events, particularly pulmonary embolism, with elevated D-dimer and coagulation activation are highly prevalent in COVID-19 patients. The pro-inflammatory cytokine storm, with elevated levels of interleukin-6 (IL-6), IL-2 receptor, and tumor necrosis factor-α, could also participate in endothelial dysfunction and leukocyte recruitment in the microvasculature. COVID-19-induced endotheliitis may explain the systemic impaired microcirculatory function in different organs in COVID-19 patients. Ongoing trials directly and indirectly target COVID-19-related endothelial dysfunctions: i.e., a virus-cell entry using recombinant angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS-2) blockade, coagulation activation, and immunomodulatory therapies, such as anti-IL-6 strategies. Studies focusing on endothelial dysfunction in COVID-19 patients are warranted as to decipher their precise role in severe SARS-CoV-2 infection and organ dysfunction and to identify targets for further interventions.
Topics: Betacoronavirus; COVID-19; Capillary Permeability; Coronavirus Infections; Endothelium, Vascular; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32546188
DOI: 10.1186/s13054-020-03062-7 -
British Journal of Pharmacology Oct 2011Endothelium-dependent contractions contribute to endothelial dysfunction in various animal models of aging, diabetes and cardiovascular diseases. In the spontaneously... (Review)
Review
Endothelium-dependent contractions contribute to endothelial dysfunction in various animal models of aging, diabetes and cardiovascular diseases. In the spontaneously hypertensive rat, the archetypal model for endothelium-dependent contractions, the production of the endothelium-derived contractile factors (EDCF) involves an increase in endothelial intracellular calcium concentration, the production of reactive oxygen species, the predominant activation of cyclooxygenase-1 (COX-1) and to a lesser extent that of COX-2, the diffusion of EDCF towards the smooth muscle cells and the subsequent stimulation of their thromboxane A2-endoperoxide TP receptors. Endothelium-dependent contractions are also observed in various models of hypertension, aging and diabetes. They generally also involve the generation of COX-1- and/or COX-2-derived products and the activation of smooth muscle TP receptors. Depending on the model, thromboxane A(2), PGH(2), PGF(2α), PGE(2) and paradoxically PGI(2) can all act as EDCFs. In human, the production of COX-derived EDCF is a characteristic of the aging and diseased blood vessels, with essential hypertension causing an earlier onset and an acceleration of this endothelial dysfunction. As it has been observed in animal models, COX-1, COX-2 or both isoforms can contribute to these endothelial dysfunctions. Since in most cases, the activation of TP receptors is the common downstream effector, selective antagonists of this receptor should curtail endothelial dysfunction and be of therapeutic interest in the treatment of cardiovascular disorders.
Topics: Animals; Cardiovascular Diseases; Cyclooxygenase 1; Cyclooxygenase 2; Endothelins; Endothelium, Vascular; Humans; Vasoconstriction
PubMed: 21323907
DOI: 10.1111/j.1476-5381.2011.01276.x -
World Journal of Gastroenterology Jan 2016Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural... (Review)
Review
Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by up-regulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-α. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flow-mediated vasodilatation (FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Endothelium, Vascular; Humans; Inflammatory Bowel Diseases; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Vasodilation
PubMed: 26811647
DOI: 10.3748/wjg.v22.i3.1067 -
Nature Clinical Practice.... Jan 2009Endothelium lining the cardiovascular system is highly sensitive to hemodynamic shear stresses that act at the vessel luminal surface in the direction of blood flow.... (Review)
Review
Endothelium lining the cardiovascular system is highly sensitive to hemodynamic shear stresses that act at the vessel luminal surface in the direction of blood flow. Physiological variations of shear stress regulate acute changes in vascular diameter and when sustained induce slow, adaptive, structural-wall remodeling. Both processes are endothelium-dependent and are systemically and regionally compromised by hyperlipidemia, hypertension, diabetes and inflammatory disorders. Shear stress spans a range of spatiotemporal scales and contributes to regional and focal heterogeneity of endothelial gene expression, which is important in vascular pathology. Regions of flow disturbances near arterial branches, bifurcations and curvatures result in complex spatiotemporal shear stresses and their characteristics can predict atherosclerosis susceptibility. Changes in local artery geometry during atherogenesis further modify shear stress characteristics at the endothelium. Intravascular devices can also influence flow-mediated endothelial responses. Endothelial flow-induced responses include a cell-signaling repertoire, collectively known as mechanotransduction, that ranges from instantaneous ion fluxes and biochemical pathways to gene and protein expression. A spatially decentralized mechanism of endothelial mechanotransduction is dominant, in which deformation at the cell surface induced by shear stress is transmitted as cytoskeletal tension changes to sites that are mechanically coupled to the cytoskeleton. A single shear stress mechanotransducer is unlikely to exist; rather, mechanotransduction occurs at multiple subcellular locations.
Topics: Adaptation, Physiological; Angioplasty; Animals; Atherosclerosis; Cardiovascular Diseases; Cytoskeleton; Endothelium, Vascular; Hemodynamics; Humans; Mechanotransduction, Cellular; Models, Cardiovascular; Phenotype; Prosthesis Design; Stents; Stress, Mechanical
PubMed: 19029993
DOI: 10.1038/ncpcardio1397 -
British Journal of Clinical Pharmacology Nov 2000Arterial endothelial dysfunction is one of the key early events in atherogenesis, preceding structural atherosclerotic changes. It is also important in the late stages... (Review)
Review
Arterial endothelial dysfunction is one of the key early events in atherogenesis, preceding structural atherosclerotic changes. It is also important in the late stages of obstructive atherosclerosis, predisposing to constriction and/or thrombosis. Endothelial function can be measured in coronary arteries and in the periphery by measuring vasomotor function after intra-arterial infusion of pharmacologic substances which enhance the release of endothelial nitric oxide. The disadvantage of these methods is their invasive nature, which generally makes them unsuitable for studies involving asymptomatic subjects. For this reason, noninvasive tests of endothelial function have been developed. In the most widely used of these, an ultrasound-based method, arterial diameter is measured in response to an increase in shear stress, which causes endothelium-dependent dilatation. Endothelial function assessed by this method correlates with invasive testing of coronary endothelial function, as well as with the severity and extent of coronary atherosclerosis. This noninvasive endothelial function testing has provided valuable insights into early atherogenesis, as well as into the potential reversibility of endothelial dysfunction by various strategies, including pharmacological agents (lipid lowering, ACE inhibition), L-arginine, antioxidants and hormones.
Topics: Arteries; Arteriosclerosis; Endothelium, Vascular; Humans; Regional Blood Flow; Ultrasonography; Vasodilation; Vasomotor System
PubMed: 11069434
DOI: 10.1046/j.1365-2125.2000.00277.x -
Current Medicinal Chemistry 2014The endothelium is a cellular monolayer that lines the inner surface of blood vessels and plays a central role in the maintenance of cardiovascular homeostasis by... (Review)
Review
The endothelium is a cellular monolayer that lines the inner surface of blood vessels and plays a central role in the maintenance of cardiovascular homeostasis by controlling platelet aggregation, vascular tone, blood fluidity and fibrinolysis, adhesion and transmigration of inflammatory cells, and angiogenesis. Endothelial dysfunctions are associated with various cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction, and cardiovascular complications of diabetes. Numerous studies have established the anti-inflammatory, anti-apoptotic, and anti-oxidant effects of hydrogen sulfide (H2S), the latest member to join the gasotransmitter family along with nitric oxide and carbon monoxide, on vascular endothelium. In addition, H2S may prime endothelial cells (ECs) toward angiogenesis and contribute to wound healing, besides to its well-known ability to relax vascular smooth muscle cells (VSMCs), and thereby reducing blood pressure. Finally, H2S may inhibit VSMC proliferation and platelet aggregation. Consistently, a deficit in H2S homeostasis is involved in the pathogenesis of atherosclerosis and of hyperglycaemic endothelial injury. Therefore, the application of H2S-releasing drugs or using gene therapy to increase endogenous H2S level may help restore endothelial function and antagonize the progression of cardiovascular diseases. The present article reviews recent studies on the role of H2S in endothelial homeostasis, under both physiological and pathological conditions, and its putative therapeutic applications.
Topics: Animals; Endothelium, Vascular; Hydrogen Sulfide; Hyperhomocysteinemia; Mice; Mice, Knockout; Nitric Oxide; Nitric Oxide Synthase Type III; Signal Transduction
PubMed: 25005182
DOI: 10.2174/0929867321666140706142930 -
Reviews in Endocrine & Metabolic... Mar 2013Vascular endothelium is an important insulin target and plays a pivotal role in the development of metabolic insulin resistance provoked by the Western lifestyle. It... (Review)
Review
Vascular endothelium is an important insulin target and plays a pivotal role in the development of metabolic insulin resistance provoked by the Western lifestyle. It acts as a "first-responder" to environmental stimuli such as nutrients, cytokines, chemokines and physical activity and regulates insulin delivery to muscle and adipose tissue and thereby affecting insulin-mediated glucose disposal by these tissues. In addition, it also regulates the delivery of insulin and other appetite regulating signals from peripheral tissues to the central nervous system thus influencing the activity of nuclei that regulate hepatic glucose production, adipose tissue lipolysis and lipogenesis, as well as food consumption. Resistance to insulin's vascular actions therefore broadly impacts tissue function and contribute to metabolic dysregulation. Moreover, vascular insulin resistance negatively impacts vascular health by affecting blood pressure regulation, vessel wall inflammation and atherogenesis thereby contributing to the burden of vascular disease seen with diabetes and metabolic syndrome. In the current review, we examined the evidence that supports the general concept of vascular endothelium as a target of insulin action and discussed the biochemical and physiological consequences of vascular insulin resistance.
Topics: Animals; Endothelium, Vascular; Humans; Insulin; Insulin Resistance; Models, Biological
PubMed: 23306779
DOI: 10.1007/s11154-012-9232-6