Sustained increase in angiopoietin-2, heparin-binding protein, and procalcitonin is associated with severe sepsis

Liu, Xiaowei; Ma, Tao; Liu, Wei; Cai, Qing Qing; Wang, Li; Song, Hongwei; Yuan, Liying; Li, Zhi

doi:10.1016/j.jcrc.2018.01.010

Cited by 17 publications

(17 citation statements)

References 32 publications

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“…Aberrant vascular leakage is the major characteristic of septic conditions. Ang2 has been associated with sepsis-related conditions [55,56,57,58,59,60] and its levels are proportional to sepsis severity [57,60]. Ang2 levels are also inversely associated with nitric oxide bioavailability.…”

Section: Role Of Ang2 In Diseasementioning

confidence: 99%

“…Ang2 knockdown by siRNA blocked neutrophil infiltration and vascular leakage, ameliorating the severity of the condition and improving survival [59]. Along with heparin-binding protein and procalcitonin, Ang2 has been recently suggested as a robust predictor of severe sepsis during the early stages of infection and prior to the appearance of the clinical symptoms [55]. Indirect acute respiratory distress syndrome (iARDS) is a life-threatening condition characterized by the loss of endothelial cell barrier function and can lead to hemorrhagic shock and sepsis.…”

Section: Role Of Ang2 In Diseasementioning

confidence: 99%

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Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology

Akwii

Sajib

Zahra

et al. 2019

Cells

376

270

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Angiopoietins 1–4 (Ang1–4) represent an important family of growth factors, whose activities are mediated through the tyrosine kinase receptors, Tie1 and Tie2. The best characterized are angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2). Ang1 is a potent angiogenic growth factor signaling through Tie2, whereas Ang2 was initially identified as a vascular disruptive agent with antagonistic activity through the same receptor. Recent data demonstrates that Ang2 has context-dependent agonist activities. Ang2 plays important roles in physiological processes and the deregulation of its expression is characteristic of several diseases. In this review, we summarize the activity of Ang2 on blood and lymphatic endothelial cells, its significance in human physiology and disease, and provide a current view of the molecular signaling pathways regulated by Ang2 in endothelial cells.

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Section: Role Of Ang2 In Diseasementioning

confidence: 99%

Section: Role Of Ang2 In Diseasementioning

confidence: 99%

Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology

Akwii

Sajib

Zahra

et al. 2019

Cells

376

270

View full text Add to dashboard Cite

show abstract

“…Likewise Fang et al [20] described a relationship between endothelial biomarkers and variations of the SOFA score during the first week after admission. Liu et al [50] also showed an association between the presence of endothelial injury on admission and severity of sepsis. More recently, Henning et al also confirmed that biomarkers of endothelial activation and inflammation in combination with emergency department physician judgment improved prediction in hospital mortality [51,52].…”

Section: Discussionmentioning

confidence: 93%

Prognostic performance of endothelial biomarkers to early predict clinical deterioration of patients with suspected bacterial infection and sepsis admitted to the emergency department

Lafon

Cazalis

Vallejo

et al. 2020

Ann. Intensive Care

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Background: The objective of this study was to evaluate the ability of endothelial biomarkers to early predict clinical deterioration of patients admitted to the emergency department (ED) with a suspected sepsis. This was a prospective, multicentre, international study conducted in EDs. Adult patients with suspected acute bacterial infection and sepsis were enrolled but only those with confirmed infection were analysed. The kinetics of biomarkers and organ dysfunction were collected at T0, T6 and T24 hours after ED admission to assess prognostic performances of sVEGFR2, suPAR and procalcitonin (PCT). The primary outcome was the deterioration within 72 h and was defined as a composite of relevant outcomes such as death, intensive care unit admission and/or SOFA score increase validated by an independent adjudication committee. Results: After adjudication of 602 patients, 462 were analysed including 124 who deteriorated (27%). On admission, those who deteriorated were significantly older (73 [60-82] vs 63 [45-78] y-o, p < 0.001) and presented significantly higher SOFA scores (2.15 ± 1.61 vs 1.56 ± 1.40, p = 0.003). At T0, sVEGFR2 (5794 [5026-6788] vs 6681 [5516-8059], p < 0.0001), suPAR (6.04 [4.42-8.85] vs 4.68 [3.50-6.43], p < 0.0001) and PCT (7.8 ± 25.0 vs 5.4 ± 17.9 ng/mL, p = 0.001) were associated with clinical deterioration. In multivariate analysis, low sVEGFR2 expression and high suPAR and PCT levels were significantly associated with early deterioration, independently of confounding parameters (sVEGFR2, OR = 1.53 [1.07-2.23], p < 0.001; suPAR, OR = 1.57 [1.21-2.07], p = 0.003; PCT, OR = 1.10 [1.04-1.17], p = 0.0019). Combination of sVEGFR2 and suPAR had the best prognostic performance (AUC = 0.7 [0.65-0.75]) compared to clinical or biological variables. Conclusions: sVEGFR2, either alone or combined with suPAR, seems of interest to predict deterioration of patients with suspected bacterial acute infection upon ED admission and could help front-line physicians in the triage process.

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“…Of these, several peptides derived from type IV collagen such as cyrostatin, the wispostatin family, and the chemokinostatin family have potent anti-angiogenic activity [97]. AXT107 (Table 2) is a 20-mer synthetic peptide derived from the non-collagenous domain of collagen IV that may be a triple threat to the pathophysiology of retinal vascular diseases: suppressing ocular neovascularization, inhibiting vascular leakage, and reducing inflammation [79,92]. AXT107 targets two pathways in a single molecule: it promotes Tie2 pathway signaling [82] while blocking VEGF pathway signaling [92].…”

Section: Targeting the Tie2 Pathway For Retinal Vascular Diseases Axt107mentioning

confidence: 99%

“…Ang2 is upregulated in settings of hypoxia [ 72 ], hyperglycemia [ 73 , 74 ] and oxidative stress [ 75 ], which are common in eyes of diabetic patients, and Ang2 levels are elevated in the vitreous of diabetic eyes [ 76 , 77 ], particularly those with retinopathy [ 78 ]. Ang2 is increased in sepsis [ 79 , 80 ]—in which increased vascular permeability is a crucial component—and Ang2 levels correlate with the severity of sepsis [ 80 ]. In contrast, Ang1 functions as an anti-permeability growth factor and promotes EC remodeling to minimize permeability [ 81 ].…”

Section: Areas Coveredmentioning

confidence: 99%

The Tie2 signaling pathway in retinal vascular diseases: a novel therapeutic target in the eye

et al. 2020

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Background Retinal vascular diseases such as neovascular age-related macular degeneration, diabetic retinopathy and/or diabetic macular edema, and retinal vein occlusion with macular edema—share several key pathophysiologic aspects including neovascularization, vascular permeability, and inflammation. The role of vascular endothelial growth factor (VEGF) in these processes, and the therapeutic benefits of VEGF inhibition, have been well characterized. Anti-VEGF therapy is highly effective for many patients but is not uniformly effective in all patients and imposes a significant treatment burden. More recently, the role of the Tie2 signaling pathway in the pathophysiology of retinal vascular diseases has been investigated, and the Tie2 pathway represents a novel therapeutic target for these conditions. Areas covered The index review describes the Tie2 pathway and its complementary role to the VEGF pathway in the angiogenesis cascade and will summarize studies of molecules in development to therapeutically modulate the Tie2 pathway in retinal vascular diseases. Conclusions Activation of the Tie2 pathway leads to downstream signaling that promotes vascular health and stability and decreases vascular permeability and inflammation. AXT107 is a collagen IV–derived synthetic peptide with a dual mechanism of action that involves suppression of VEGF signaling and activation of the Tie2 pathway; these actions are accomplished by AXT107 binding to and disrupting different integrin, leading to blockade of the VEGF receptor and rearrangement of cellular Tie2 rendering it susceptible to Ang2 agonism. Other Tie2 agonist compounds are also in development, including faricimab and razuprotafib. Tie2 activation only modestly impacts angiogenesis on its own but significantly potentiates VEGF suppression. Co-regulation of the VEGF and Tie2 signaling pathways has the potential to improve functional and structural outcomes in eyes with retinal vascular diseases.

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Sustained increase in angiopoietin-2, heparin-binding protein, and procalcitonin is associated with severe sepsis

Cited by 17 publications

References 32 publications

Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology

Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology

Prognostic performance of endothelial biomarkers to early predict clinical deterioration of patients with suspected bacterial infection and sepsis admitted to the emergency department

The Tie2 signaling pathway in retinal vascular diseases: a novel therapeutic target in the eye

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