Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential

Becker, Bernhard F.; Chappell, Daniel; Bruegger, Dirk; Annecke, Thorsten; Jacob, Matthias

doi:10.1093/cvr/cvq137

Cited by 355 publications

(430 citation statements)

References 98 publications

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“…It interacts with plasma proteins and lipids [9]. The composition and dimensions of the glycocalyx fluctuate as it continuously replaces material sheared by flowing plasma [10], while throughout the vasculature, the thickness varies 10-fold, between 0.1 and 1 lm [11].…”

Section: Structure Of the Endothelial Glycocalyxmentioning

confidence: 99%

“…However, this model is inadequate, with experiments over the past 25 years revealing additional processes in action. Starling was not aware of the reduction in fluid extravasation by the glycocalyx, which has revised the original Starling equation [2,8,11].…”

Section: Physiology Of the Endothelial Surface Layermentioning

confidence: 99%

“…2). The oncotic pressure differences across the endothelial surface layer are tightly regulated and reach equilibrium very quickly, thereby leading to less fluid filtration [11,15,16].…”

Section: Physiology Of the Endothelial Surface Layermentioning

confidence: 99%

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The endothelial glycocalyx: a review of the vascular barrier

Alphonsus¹,

2014

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SummaryThe endothelial glycocalyx is an important part of the vascular barrier. The glycocalyx is intimately linked to the homoeostatic functions of the endothelium. Damage to the glycocalyx precedes vascular pathology. In the first part of this paper, we have reviewed the structure, physiology and pathology of the endothelial glycocalyx, based on a literature search of the past five years. In the second part, we have systematically reviewed interventions to protect or repair the glycocalyx. Glycocalyx damage can be caused by hypervolaemia and hyperglycaemia and can be prevented by maintaining a physiological concentration of plasma protein, particularly albumin.

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Section: Structure Of the Endothelial Glycocalyxmentioning

confidence: 99%

Section: Physiology Of the Endothelial Surface Layermentioning

confidence: 99%

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The endothelial glycocalyx: a review of the vascular barrier

Alphonsus¹,

2014

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“…Endothelial glycocalyx is shed in response to inflammation, oxidized LDL, abnormal blood shear stress, TNF-␣, ischemia-perfusion injury, and redox stress. Vascular EC is one of the earliest sites of injury during inflammation, and the loss of glycocalyx increases intravascular leukocyte and platelet adhesion to ECs and activates inflammatory and coagulatory cascades (9,37,122). In response to infection and inflammatory mediators, ECs secrete increased amounts of interleukin (IL)-6, and upregulate intracellular adhesion molecule and vascular adhesion molecule, which spread over the surface of ECs.…”

Section: Endothelial Cell Functionmentioning

confidence: 99%

Pathogenesis of pulmonary hypertension: a case for caveolin-1 and cell membrane integrity

Mathew

2014

American Journal of Physiology-Heart and Circulatory Physiology

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Mathew R. Pathogenesis of pulmonary hypertension: a case for caveolin-1 and cell membrane integrity. Am J Physiol Heart Circ Physiol 306: H15-H25, 2014. First published October 25, 2013 doi:10.1152/ajpheart.00266.2013.-Pulmonary hypertension (PH) is a progressive disease with a high morbidity and mortality rate. Despite important advances in the field, the precise mechanisms leading to PH are not yet understood. Main features of PH are loss of vasodilatory response, the activation of proliferative and antiapoptotic pathways leading to pulmonary vascular remodeling and obstruction, elevated pressure and right ventricular hypertrophy, resulting in right ventricular failure and death. Experimental studies suggest that endothelial dysfunction may be the key underlying feature in PH. Caveolin-1, a major protein constituent of caveolae, interacts with several signaling molecules including the ones implicated in PH and modulates them. Disruption and progressive loss of endothelial caveolin-1 with reciprocal activation of proliferative pathways occur before the onset of PH, and the rescue of caveolin-1 inhibits proliferative pathways and attenuates PH. Extensive endothelial damage/loss occurs during the progression of the disease with subsequent enhanced expression of caveolin-1 in smooth muscle cells. This caveolin-1 in smooth muscle cells switches from being an antiproliferative factor to a proproliferative one and participates in cell proliferation and cell migration, possibly leading to irreversible PH. In contrast, the disruption of endothelial caveolin-1 is not observed in the hypoxia-induced PH, a reversible form of PH. However, proliferative pathways are activated in this model, indicating caveolin-1 dysfunction. Thus disruption or dysfunction of endothelial caveolin-1 leads to PH, and the status of caveolin-1 may determine the reversibility versus irreversibility of PH. This article reviews the role of caveolin-1 and cell membrane integrity in the pathogenesis and progression of PH.caveolin-1; endothelial cells; pulmonary hypertension; smooth muscle cells THIS ARTICLE is part of a collection on Pathophysiology of Hypertension. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.In 1891, Ernst von Romberg, a German physician, described histological changes in pulmonary hypertension (PH) as pulmonary vascular sclerosis (30). Since then remarkable advances have been made in the understanding of PH, but the pathogenesis of PH still remains elusive, partly because a number of diseases can lead to PH and multiple signaling pathways are implicated in PH. Furthermore, not all signaling pathways are activated in a given patient, and their activation may depend on the stage of the disease. Experimental data suggest that the vascular changes occur before the onset of PH (47,48). Therefore, it is not surprising that by the time the diagnosis of PH is made, most patients have significant pathological changes in pulmonary vasculatu...

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“…Glycocalyx damage is associated with pathophysiological sequelae, such as capillary leakage and edema formation, accelerated inflammation, platelet activation and hypercoagulability, and loss of vascular responsiveness. 15,16 It is unknown whether glycocalyx lesions have any role in leptospirosis-related AKI pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Libório¹,

Braz²,

Seguro³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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Abstract. Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinaseassociated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKIassociated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage.

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Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential

Cited by 355 publications

References 98 publications

The endothelial glycocalyx: a review of the vascular barrier

The endothelial glycocalyx: a review of the vascular barrier

Pathogenesis of pulmonary hypertension: a case for caveolin-1 and cell membrane integrity

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

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