Angiopoietin-2, Marker and Mediator of Endothelial Activation With Prognostic Significance Early After Trauma?

Ganter, Michael T.; Cohen, Mitchell J.; Brohi, Karim; Chesebro, Brian B.; Staudenmayer, Kristan; Rahn, Pamela; Christiaans, Sarah C.; Bir, Natasha D.; Pittet, Jean–François

doi:10.1097/sla.0b013e318162d616

Cited by 113 publications

(107 citation statements)

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“…Notably, elevated Ang2 plasma levels have been found to correlate with the activation of the complement pathway in severe trauma patients, particularly in the alternative cascade. 39 An elevated placental C5a level also has been found to be positively associated with Ang2. 40 In addition, TNF-a, an inflammatory mediator, increased the mRNA and protein levels of Ang2 in cultured choroidal endothelial cells from surgically excised CNV membranes.…”

Section: Discussionmentioning

confidence: 98%

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations

Brelén

Tsujikawa

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Ma L, Brelen ME, Tsujikawa M, et al. Identification of ANGPT2 as a new gene for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in the Chinese and Japanese populations. Invest Ophthalmol Vis Sci. 2017;58:107658: -108358: . DOI:10.1167 PURPOSE. We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS.A total of 34 haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed.RESULTS. In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction.CONCLUSIONS. This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.Keywords: ANGPT2, gene association, age-related macular degeneration, polypoidal choroidal vasculopathy, gene-gene interaction A ge-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly, especially in developed countries. Neovascular AMD (nAMD), a major form of advanced AMD characterized by choroidal neovascularization (CNV), accounts for the majority of severe visual loss in AMD patients. Polypoidal choroidal vasculopathy (PCV) is a macular disease characterized by polyp-like lesions in the choroidal vessels, which are best seen in indocyanine green angiography (ICGA).1 Polypoidal choroidal vasculopathy and nAMD have similarities in clinical manifestations. For example, they can cause submacular hemorrhage, exudation, and scarring, leading to central vision loss. Interestingly, CNV and PCV can present concurrently in approximately 3.23% of patients, 2 suggesting that they may have a shared mechanism. However, while the prevalence of nAMD (approximately 0.46%) is similar between Caucasian and Asian populations, 3 the prevalence of PCV is approximately 3-fold higher in Asians than in Caucasians, 4 suggesting an ethnic background is related to the occurrence of PCV. Moreover, nAMD and PCV respond differentl...

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Section: Discussionmentioning

confidence: 98%

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations

Brelén

Tsujikawa

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…A recent review [22 ] describes six key interacting mechanisms that lead to coagulopathy in trauma patients: tissue trauma, shock, hemodilution, hypothermia, acidemia, and inflammation. The systemic inflammatory response associated with severe injury results in the activation of cellular and humoral mediators much earlier than previously thought [23]. Tissue damage causes activation and depletion of clotting factors and hyperfibrinolysis through endothelial injury, and hypothermia and acidemia inhibit protease activity and decrease platelet function [24][25][26][27].…”

Section: Coagulopathy Of Traumamentioning

confidence: 99%

New developments in massive transfusion in trauma

Greer

Rhynhart

Gupta

et al. 2010

Current Opinion in Anaesthesiology

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“…Die Wechselwirkungen zwischen Ent zündungsreaktion und Gerinnung sind erheblich ausgeprägter als bisher ange nommen [29]. Aktivierte Gerinnungs faktoren induzieren eine Inflammati on durch proteaseaktivierte Rezeptoren auf Zelloberflächen, Komplementakti vierung und Freisetzung von Plättchen granula [34].…”

Section: Inflammationunclassified

Coagulation management in the treatment of multiple trauma

2009

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In recent years a new understanding of trauma-associated hemorrhaging and trauma-induced coagulopathy has been achieved. This coagulopathy is multifactorial with the predominant mechanisms being tissue trauma, shock and hypoperfusion which can lead to hyperfibrinolysis by activation of the endothelium. Routinely tested coagulation parameters, such as prothrombin time and partial thromboplastin time, are frequently employed for decision making but remain problematic as they do not give any information on clot stability, lysis or platelet function. Thrombelastometry seems to be a useful alternative. A pro-active anticipatory approach is required for a successful outcome to be achieved as rescue correction is more difficult than prevention. While the pathophysiological conception of causal relationship of the mentioned therapeutic options is conclusive, an evidence-based validation by randomized controlled studies is mostly lacking. The emergency and anesthesiological concept of damage control resuscitation consists of limiting volume therapy with crystalloids and colloids to reach a mean arterial pressure > or =65 mmHg (higher for head injuries), active (re-)warming management, the prevention of a pH< or =7.2 and a base excess (BE) < or =-6 mmol/l. The early and sufficient application of hemostatic drugs is essential. Because erythrocytes play a substantial role in the coagulation process, hemoglobin (Hb) values of around 6. 2 mmol/l (10 g/dl) and/or a hematocrit of 30% should be strived for when massive non-arrested hemorrhaging occurs. After severe multiple trauma a fibrinogen deficit develops and must be adequately compensated. If coagulation therapy is carried out using fresh frozen plasma sufficient quantities (20-30 ml/kgBW) must be administered to correspondingly raise the coagulation factors. Prothrombin complex concentrates can be helpful to optimize thrombin generation during severe hemorrhaging. Because hyperfibrinolysis occurs more often than previously assumed during severe trauma, an anti-fibrinolytic therapy should be used especially for patients with an instable circulation. The platelet count should not go below 100,000/microl when hemorrhaging occurs after multiple trauma. For thrombocytopathic patients with diffuse bleeding desmopressin (DDAVP) is a therapeutic option and the "off label" use of recombinant activated factor VIIa (rFVIIa) remains an option for individual situations with stringent indications and when the above named measures to optimize the coagulation situation have been taken.

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Angiopoietin-2, Marker and Mediator of Endothelial Activation With Prognostic Significance Early After Trauma?

Cited by 113 publications

References 50 publications

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations

New developments in massive transfusion in trauma

Coagulation management in the treatment of multiple trauma

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