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International Journal of Biological... 2013Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial... (Review)
Review
Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.
Topics: Disease; Endothelium, Vascular; Humans
PubMed: 24250251
DOI: 10.7150/ijbs.7502 -
Nature Reviews. Nephrology Feb 2019The kidney harbours different types of endothelia, each with specific structural and functional characteristics. The glomerular endothelium, which is highly fenestrated... (Review)
Review
The kidney harbours different types of endothelia, each with specific structural and functional characteristics. The glomerular endothelium, which is highly fenestrated and covered by a rich glycocalyx, participates in the sieving properties of the glomerular filtration barrier and in the maintenance of podocyte structure. The microvascular endothelium in peritubular capillaries, which is also fenestrated, transports reabsorbed components and participates in epithelial cell function. The endothelium of large and small vessels supports the renal vasculature. These renal endothelia are protected by regulators of thrombosis, inflammation and complement, but endothelial injury (for example, induced by toxins, antibodies, immune cells or inflammatory cytokines) or defects in factors that provide endothelial protection (for example, regulators of complement or angiogenesis) can lead to acute or chronic renal injury. Moreover, renal endothelial cells can transition towards a mesenchymal phenotype, favouring renal fibrosis and the development of chronic kidney disease. Thus, the renal endothelium is both a target and a driver of kidney and systemic cardiovascular complications. Emerging therapeutic strategies that target the renal endothelium may lead to improved outcomes for both rare and common renal diseases.
Topics: Endothelial Cells; Endothelium; Humans; Kidney; Kidney Diseases
PubMed: 30607032
DOI: 10.1038/s41581-018-0098-z -
Clinics in Haematology Jun 1981Endothelium, platelets and macrophages can each provide growth factors that may participate in atherosclerotic lesion initiation or progression, or both. These mitogens,... (Review)
Review
Endothelium, platelets and macrophages can each provide growth factors that may participate in atherosclerotic lesion initiation or progression, or both. These mitogens, coupled with alternations in endothelial integrity or function resulting from a variety of different risk-associated factors, such as hyperlipidaemia, hypertension, tobacco smoke, antibodies, infections, or homocystinaemia, may provide the basis for the intimal proliferative smooth muscle cell response of atherosclerosis. Platelets, endothelium or macrophages may be important in lesion initiation and progression in some circumstances but not in others, depending upon the extent and type of endothelial "injury'.
Topics: Animals; Arteriosclerosis; Blood Platelets; Cell Division; Endothelium; Epidermal Growth Factor; Humans; Lipoproteins, LDL; Macrophages; Muscle, Smooth
PubMed: 7032778
DOI: No ID Found -
Respiratory Research Apr 2024The success of lung transplantation is limited by the high rate of primary graft dysfunction due to ischemia-reperfusion injury (IRI). Lung IRI is characterized by a... (Review)
Review
The success of lung transplantation is limited by the high rate of primary graft dysfunction due to ischemia-reperfusion injury (IRI). Lung IRI is characterized by a robust inflammatory response, lung dysfunction, endothelial barrier disruption, oxidative stress, vascular permeability, edema, and neutrophil infiltration. These events are dependent on the health of the endothelium, which is a primary target of IRI that results in pulmonary endothelial barrier dysfunction. Over the past 10 years, research has focused more on the endothelium, which is beginning to unravel the multi-factorial pathogenesis and immunologic mechanisms underlying IRI. Many important proteins, receptors, and signaling pathways that are involved in the pathogenesis of endothelial dysfunction after IR are starting to be identified and targeted as prospective therapies for lung IRI. In this review, we highlight the more significant mediators of IRI-induced endothelial dysfunction discovered over the past decade including the extracellular glycocalyx, endothelial ion channels, purinergic receptors, kinases, and integrins. While there are no definitive clinical therapies currently available to prevent lung IRI, we will discuss potential clinical strategies for targeting the endothelium for the treatment or prevention of IRI. The accruing evidence on the essential role the endothelium plays in lung IRI suggests that promising endothelial-directed treatments may be approaching the clinic soon. The application of therapies targeting the pulmonary endothelium may help to halt this rapid and potentially fatal injury.
Topics: Humans; Lung; Reperfusion Injury; Endothelium; Lung Transplantation; Lung Injury
PubMed: 38637760
DOI: 10.1186/s12931-024-02776-4 -
Advanced Science (Weinheim,... Jun 2023Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the...
Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While cancer research has mostly focused on the biomechanical interactions between tumor cells (TCs) and ECM, particularly at the primary tumor site, very little is known about the mechanical properties of endothelial cells and the subendothelial ECM and how they contribute to the extravasation process. Here, an integrated experimental and theoretical framework is developed to investigate the mechanical crosstalk between TCs, endothelium and subendothelial ECM during in vitro cancer cell extravasation. It is found that cancer cell actin-rich protrusions generate complex push-pull forces to initiate and drive TEM, while transmigration success also relies on the forces generated by the endothelium. Consequently, mechanical properties of the subendothelial ECM and endothelial actomyosin contractility that mediate the endothelial forces also impact the endothelium's resistance to cancer cell transmigration. These results indicate that mechanical features of distant tissues, including force interactions between the endothelium and the subendothelial ECM, are key determinants of metastatic organotropism.
Topics: Transendothelial and Transepithelial Migration; Endothelial Cells; Endothelium; Actins; Mechanical Phenomena; Neoplasms
PubMed: 37051804
DOI: 10.1002/advs.202206554 -
Archives of Pathology & Laboratory... Feb 1977The renewed interest in endothelial function is based partly on success with tissue culture of endothelial cells. Endothelium functions primarily in the control of blood... (Review)
Review
The renewed interest in endothelial function is based partly on success with tissue culture of endothelial cells. Endothelium functions primarily in the control of blood vessel wall permeability and in the provision of a blood-compatible lining surface. Recent findings indicate that endothelial cells are active metabolically in ways that may help prevent thrombosis. Endothelium actively degrades several different vasoactive compounds that circulate in blood and that can serve as platelet-aggregating agents. Endothelium also contains an inhibitor of platelet function and an activator of plasminogen, both of which can be released from the cell in response to appropriate stimuli. While intact endothelium functions primarily in prevention of thrombosis, damaged endothelium can contribute greatly to thrombus formation. Release of prostaglandins, adenine nucleotides, and other intracellular components from damaged endothelium can enhance platelet aggregation. Damaged endothelium may not function effectively in removal of vasoactive agents and may not release effective quantities of the inhibitor of platelet function or the activator of plasminogen. Altered endothelium exhibits tissue-factor activity, which can activate the extrinsic blood coagulation-system cascade. Finally, altered endothelial cells may contract and expose basement membrane to blood, thus enhancing thrombosis.
Topics: Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Endothelium; Hemostasis; Humans; Leukocytes; Plasminogen Activators; Platelet Aggregation; Thrombin; Thrombosis
PubMed: 319773
DOI: No ID Found -
Seminars in Thrombosis and Hemostasis Apr 2010The endothelium is composed of specialized epithelial cells that line the vasculature, the lymph vessels, and the heart. These endothelial cells are characterized by... (Review)
Review
The endothelium is composed of specialized epithelial cells that line the vasculature, the lymph vessels, and the heart. These endothelial cells are characterized by their stratification and are connected via intercellular junctions that confer specific permeability. Although all endothelium acts as a barrier, considerable heterogeneity exists among different organs and even within vessels. During development, the endothelial cells are specified before they migrate to their final destination, and then they commit to an arterial or venous fate. From the venous endothelial cell population, a subset of cells is further specified as lymphatic endothelium. The endothelium can be highly permeable, as in the lymph vessels, or impenetrable, as in the blood-brain barrier. These differences arise during development and are orchestrated through a series of signaling pathways. This review details how endothelial cells arise and are directed to their specific fate, specifically targeting what differentiates endothelial populations.
Topics: Cell Differentiation; Endothelium; Permeability; Signal Transduction
PubMed: 20490975
DOI: 10.1055/s-0030-1253446 -
Current Atherosclerosis Reports Sep 2023The goal of this article is to characterize the endothelium's role in the development of hypertension and dyslipidemia and to point out promising therapeutic directions. (Review)
Review
PURPOSE OF REVIEW
The goal of this article is to characterize the endothelium's role in the development of hypertension and dyslipidemia and to point out promising therapeutic directions.
RECENT FINDINGS
Dyslipidemia may facilitate the development of hypertension, whereas the collaboration of these two silent killers potentiates the risk of atherosclerosis. The common pathophysiological denominator for hypertension and dyslipidemia is endothelial cell dysfunction, which manifests as dysregulation of homeostasis, redox balance, vascular tone, inflammation, and thrombosis. Treatment focused on mediators acting in these processes might be groundbreaking. Metabolomic research on hypertension and dyslipidemia has revealed new therapeutic targets. State-of-the-art solutions integrating interview, clinical examination, innovative imaging, and omics profiles along with artificial intelligence have been already shown to improve patients' risk stratification and treatment. Pathomechanisms underlying hypertension and dyslipidemia take place in the endothelium. Novel approaches involving endothelial biomarkers and bioinformatics advances could open new perspectives in patient management.
Topics: Humans; Artificial Intelligence; Hypertension; Dyslipidemias; Crime; Endothelium
PubMed: 37594602
DOI: 10.1007/s11883-023-01132-z -
Texas Heart Institute Journal 1994The early observations of an apparent anomalous action of acetylcholine on the regulation of vascular tone in vivo and in vitro were found to be a reflection of the... (Review)
Review
The early observations of an apparent anomalous action of acetylcholine on the regulation of vascular tone in vivo and in vitro were found to be a reflection of the intactness of the endothelium in vivo. An intact endothelium mediates relaxation of smooth muscle in response to acetylcholine, whereas endothelium-denuded blood vessels exposed to this agonist often exhibit vasoconstriction. The vasodilation is mediated by the actions of the endothelium-derived relaxing factors nitric oxide and prostacyclin. In addition, endothelial cells release endothelium-derived hyperpolarizing factor, which regulates potassium-channel opening in vascular smooth muscle. The chemical nature of this molecule remains to be elucidated. Many of the physiologic stimulants for endothelium-derived relaxing factor production are released by aggregating platelets, and the significance of the endothelium's vasoprotective role becomes apparent when the mechanisms and consequences of platelet agglutination are studied. Damage to the endothelium, however minor, results in the loss of this protective function and is associated with an impaired response to serotonin of G-protein coupled receptors. In the presence of risk factors such as elevated serum cholesterol, the consequences of an impaired endothelial function are greatly enhanced. Age-related changes in endothelial responsiveness may account for the prevalence of cardiovascular disease in human beings over the age of 30 years.
Topics: Blood Platelets; Endothelins; Endothelium, Vascular; Epoprostenol; Humans; In Vitro Techniques; Nitric Oxide
PubMed: 8180513
DOI: No ID Found -
Sports Medicine (Auckland, N.Z.) Oct 1996This review discusses the role of the endothelium in the regulation of coronary vascular function. The role of endothelium-mediated mechanisms at rest, during exercise,... (Review)
Review
This review discusses the role of the endothelium in the regulation of coronary vascular function. The role of endothelium-mediated mechanisms at rest, during exercise, in exercise training-induced adaptations of coronary function and in the presence of coronary heart disease (CHD) are examined. Mechanisms of control of coronary blood flow are briefly discussed with emphasis on endothelium-mediated control of vascular resistance. The concept that the relative importance of vascular control mechanisms differs as a function of position along the coronary arterial tree is developed and discussed. Metabolic, myogenic and endothelium-mediated control systems contribute in parallel to regulating coronary blood flow. The relative importance of these mechanisms varies throughout the coronary arterial tree. Endothelium-dependent vasodilation contributes to maintenance of resting coronary blood flow but the endothelium's role in dilation of small resistance arteries, thereby increasing coronary blood flow during exercise, remains in question. In contrast, the endothelium plays an essential role in dilation of the conduit coronary arteries during exercise. Atherosclerosis and CHD convert this exercise-induced dilation to a vasoconstriction, apparently due to endothelium dysfunction. Long term increases in physical activity and exercise training alter the control of coronary blood flow. Adaptations in endothelium-mediated control play a role in these changes. However, the effects of the mode, frequency, and intensity of exercise training bouts and duration of training on adaptive changes in endothelial function have not been established. The role of the endothelium in control of the permeability characteristics of the exchange vessels in the coronary circulation is discussed. Current evidence indicates that vascular permeability is a dynamic characteristic of the vessel wall that is controlled, at least in part, by endothelium-dependent phenomena. Also, preliminary results indicate that exercise training alters microvessel permeability and the control of permeability in the coronary circulation. Further research is needed to provide clarification of the effects of exercise training on coronary endothelial control of vascular resistance and vascular permeability in atherosclerosis and CHD.
Topics: Adaptation, Physiological; Coronary Circulation; Endothelium, Vascular; Humans; Physical Education and Training
PubMed: 8898457
DOI: 10.2165/00007256-199622040-00003