Vascular Fragility and the Endothelial Glycocalyx in the Tissues Lining the Healthy Gingival Crevice

Townsend, David; D’Aiuto, Francesco; Deanfield, John

doi:10.1902/jop.2016.150568

Cited by 3 publications

(4 citation statements)

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“…67,73 Thus, loss of ESG function has been shown to alter microvascular flow, permeability and immune function. 74,75 In this respect, many reports discovered that shedding of ESG components is a hallmark of various pathological conditions such as tumour necrosis factora (TNF-a)-induced inflammation, 76 haemorrhagic shock, 77 endotoxaemia 78 and hyperglycaemia. 79 Damaged ESG was also reported in clinical conditions following trauma, 80 ischaemia reperfusion 81 and surgery.…”

Section: Agonistsmentioning

confidence: 99%

“…Most importantly, ESG may contribute to the maintenance of endothelial function by limiting the adhesion of leucocytes and platelets to the surface of endothelial cell . Thus, loss of ESG function has been shown to alter microvascular flow, permeability and immune function . In this respect, many reports discovered that shedding of ESG components is a hallmark of various pathological conditions such as tumour necrosis factor‐ α (TNF‐ α )‐induced inflammation, haemorrhagic shock, endotoxaemia and hyperglycaemia .…”

Section: Structure Of the Endothelial Barriermentioning

confidence: 99%

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Mind the gap: mechanisms regulating the endothelial barrier

2017

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The endothelial barrier consists of intercellular contacts localized in the cleft between endothelial cells, which is covered by the glycocalyx in a sievelike manner. Both types of barrier-forming junctions, i.e. the adherens junction (AJ) serving mechanical anchorage and mechanotransduction and the tight junction (TJ) sealing the intercellular space to limit paracellular permeability, are tethered to the actin cytoskeleton. Under resting conditions, the endothelium thereby builds a selective layer controlling the exchange of fluid and solutes with the surrounding tissue. However, in the situation of an inflammatory response such as in anaphylaxis or sepsis intercellular contacts disintegrate in post-capillary venules leading to intercellular gap formation. The resulting oedema can cause shock and multi-organ failure. Therefore, maintenance as well as coordinated opening and closure of interendothelial junctions is tightly regulated. The two principle underlying mechanisms comprise spatiotemporal activity control of the small GTPases Rac1 and RhoA and the balance of the phosphorylation state of AJ proteins. In the resting state, junctional Rac1 and RhoA activity is enhanced by junctional components, actin-binding proteins, cAMP signalling and extracellular cues such as sphingosine-1-phosphate (S1P) and angiopoietin-1 (Ang-1). In addition, phosphorylation of AJ components is prevented by junction-associated phosphatases including vascular endothelial protein tyrosine phosphatase (VE-PTP). In contrast, inflammatory mediators inhibiting cAMP/Rac1 signalling cause strong activation of RhoA and induce AJ phosphorylation finally leading to endocytosis and cleavage of VE-cadherin. This results in dissolution of TJs the outcome of which is endothelial barrier breakdown.

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Section: Agonistsmentioning

confidence: 99%

Section: Structure Of the Endothelial Barriermentioning

confidence: 99%

Mind the gap: mechanisms regulating the endothelial barrier

2017

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“…Our study only investigated the development of gingivitis and any link to periodontitis is purely theoretical; in addition to this, it is important to note that the small number of participants has made it impossible to remove possible confounding factors in the statistical analysis such as age, sex, and ethnicity. However, recent 3-dimensional histochemical analyses and imaging studies of the human gingiva have confirmed the presence of many tortuous dilated capillaries and shown some evidence of the loss of the endothelial glycocalyx and low oxygen saturation in afferent and efferent arms of the capillary loop, also suggesting a shift to venular capillaries [ 19 20 ]. The present study has confirmed evidence from previous studies of a disparity in gingival flux in different participants after 3 weeks of plaque accumulation, and we also found evidence of the development of venous capillaries, which are replaced by arteriolar capillaries during tissue recovery.…”

Section: Discussionmentioning

confidence: 99%

“…However, the anatomy of the human gingival vasculature has only recently been fully described in detail with little functional assessment [ 19 ]. We have previously shown that capillary loops in tissues affected by periodontal breakdown contain predominantly deoxygenated blood and that these loops have no evidence of an intact glycocalyx, suggesting the presence of venous capillary loops [ 20 21 ]. This has increased our knowledge of the disease process, but gives no indication of why some people develop periodontal breakdown whilst others do not progress beyond gingival inflammation.…”

Section: Introductionmentioning

confidence: 99%

Identification of venular capillary remodelling: a possible link to the development of periodontitis?

Townsend

2022

J Periodontal Implant Sci

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Purpose The present study measured changes in arteriolar and venular capillary flow and structure in the gingival tissues during the development of plaque-induced gingival inflammation by combining dynamic optical coherence tomography (OCT), laser perfusion, and capillaroscopic video imaging. Methods Gingival inflammation was induced in 21 healthy volunteers over a 3-week period. Gingival blood flow and capillary morphology were measured by dynamic OCT, laser perfusion imaging, and capillaroscopy, including a baseline assessment of capillary glycocalyx thickness. Venular capillary flow was estimated by analysis of the perfusion images and mean blood velocity/acceleration in the capillaroscopic images. Readings were recorded at baseline and weekly over the 3 weeks of plaque accumulation and 2 weeks after brushing was resumed. Results Perfusion imaging demonstrated a significant reduction of gingival blood flow after 1 and 2 weeks of plaque accumulation ( P <0.05), but by 3 weeks of plaque accumulation there was a more mixed picture, with reduced flow in some participants and increased flow in others. Participants with reduced flux at 3 weeks also demonstrated venular-type flow as determined by perfusion images and evidence of the development of venular capillaries as assessed by the velocity/acceleration ratio in capillaroscopic images. After brushing resumed, these venular capillaries were broken down and replaced by arteriolar capillaries. Conclusions After 3 weeks of plaque accumulation, there was wide variation in microvascular reactions between the participants. Reduced capillary flow was associated with the development of venular capillaries in some individuals. This is noteworthy, as an early increase in venous capillaries is a key vascular feature of cardiovascular disease, psoriasis, Sjögren syndrome, and rheumatoid arthritis—diseases with a significant association with the development of severe gingival inflammation, which leads to periodontitis. Future investigations of microvascular changes in gingival inflammation might benefit from accurate capillary flow velocity measurements to assess the development of venular capillaries.

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