Effects of C1 inhibitor on endothelial cell activation in a rat hind limb ischemia-reperfusion injury model

Zhang, Shengye; Shaw-Boden, Jane; Banz, Yara; Bongoni, Anjan K.; Taddeo, Adriano; Spirig, Rolf; Nolte, Marc W.; Cowan, Peter J.; Rieben, Robert

doi:10.1016/j.jvs.2017.10.072

Cited by 23 publications

(10 citation statements)

References 48 publications

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“…Immunofluorescence stainings were performed for CD31 and vascular endothelial (VE)-Cadherin on tissue samples taken on POD 0 ( a) and POD 7 ( b , c and d ), following the protocol described by Zhang et al [ 39 ]. Skin samples from the different regions were rinsed in PBS, blotted dry, embedded in OCT matrix (Tissue-Tek; Sakura Finetek Europe BV, Leiden, The Netherlands), and stored at −25°C until cryosections (5 μm tick) were made.…”

Section: Methodsmentioning

confidence: 99%

Bioactive nanoparticle-based formulations increase survival area of perforator flaps in a rat model

et al. 2018

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BackgroundDistal flap necrosis is a frequent complication of perforator flaps. Advances in nanotechnology offer exciting new therapeutic approaches. Anti-inflammatory and neo-angiogenic properties of certain metal oxides within the nanoparticles, including bioglass and ceria, may promote flap survival. Here, we explore the ability of various nanoparticle formulations to increase flap survival in a rat model.Materials and methodsA 9 x 3 cm dorsal flap based on the posterior thigh perforator was raised in 32 Lewis rats. They were divided in 4 groups and treated with different nanoparticle suspensions: I–saline (control), II–Bioglass, III–Bioglass/ceria and IV–Zinc-doped strontium-substituted bioglass/ceria. On post-operative day 7, planimetry and laser Doppler analysis were performed to assess flap survival and various samples were collected to investigate angiogenesis, inflammation and toxicity.ResultsAll nanoparticle-treated groups showed a larger flap survival area as compared to the control group (69.9%), with groups IV (77,3%) and II (76%) achieving statistical significance. Blood flow measurements by laser Doppler analysis showed higher perfusion in the nanoparticle-treated flaps. Tissue analysis revealed higher number of blood vessels and increased VEGF expression in groups II and III. The cytokines CD31 and MCP-1 were decreased in groups II and IV.ConclusionsBioglass-based nanoparticles exert local anti-inflammatory and neo-angiogenic effects on the distal part of a perforator flap, increasing therefore its survival. Substitutions in the bioglass matrix and trace metal doping allow for further tuning of regenerative activity. These results showcase the potential utility of these nanoparticles in the clinical setting.

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Section: Methodsmentioning

confidence: 99%

Bioactive nanoparticle-based formulations increase survival area of perforator flaps in a rat model

et al. 2018

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“…To specifically characterize the sequence of transcriptional events during the transition to chronic kidney injury, we performed a pseudotime analysis including only samples collected at 3 and 12 months and based on genes differentially expressed in communities A and B ( Figure 3E). Among the most significantly differentially expressed genes, we found genes involved in cell death (e.g., DAD1, ANXA5) and complement regulation (e.g., CD59, SERPING1), which progressively increased with pseudotime (28). The upregulation of genes related to fibrosis (e.g., COL1A2, DCN, MMP2; Figure 3, F and G) was a late event, coincident with the activation of genes regulating lymphocyte trafficking (e.g., CCL19, CCL21).…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

Transcriptional trajectories of human kidney injury progression

Cippà¹,

Sun²,

Liu³

et al. 2018

JCI Insight

108

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“…Panagiotou et al [5] have reviewed clinical trials using the complement inhibitor C1 esterase inhibitor (C1INH) in human myocardial I/R injury [30,31]. C1INH is an obvious first choice in the search for treatment against IR injuries, as it has an additional effect by preventing cells to alter into procoagulatory and anti-fibrolytic states [32]. The most recent clinical study, a randomized clinical trial with 78 STEMI patients, showed a significantly better…”

Section: Discussionmentioning

confidence: 99%

Circulating lectin pathway proteins do not predict short-term cardiac outcomes after myocardial infarction

Holt

Østergaard

Thiel

et al. 2019

Clinical and Experimental Immunology

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Despite improvements in treatment, coronary artery disease is still responsible for one-third of all deaths globally, due predominantly to myocardial infarction (MI) and stroke. There is an important potential in developing new strategies for treatment of patients with these conditions. Inflammation, and in particular the actions of the complement system, has emerged as part of the pathogenesis in reperfusion injury in patients with MI. To further qualify this, we examined the association between the plasma levels of lectin pathway proteins and myocardial end-points, left ventricular ejection fraction (LVEF) and infarct size in a cohort of patients with ST-elevation myocardial infarction (STEMI). A blood sample was drawn the day after percutaneous coronary intervention from 73 patients with STEMI. The primary end-points, LVEF and infarct size, were measured with magnetic resonance imaging 6-9 days after the infarct. Complement pattern-recognition molecules of the lectin pathway (mannanbinding lectin, H-ficolin, L-ficolin and M-ficolin) were analysed along with soluble membrane attack complex (sMAC) and C-reactive protein (CRP)in plasma with immunofluorometric assays <50%. CRP correlated negatively with LVEF, regression coefficient = -0·17 (P = 0·01). None of the lectin pathway proteins correlated to LVEF or infarct size, nor did soluble membrane attack complex (sMAC). There were no differences in plasma levels of these complement proteins when comparing patients with ejection fraction <50% to patients with ejection fraction <50%. Pattern-recognition molecules of the lectin pathway and sMAC do not predict shortterm cardiac outcomes after MI.

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Effects of C1 inhibitor on endothelial cell activation in a rat hind limb ischemia-reperfusion injury model

Cited by 23 publications

References 48 publications

Bioactive nanoparticle-based formulations increase survival area of perforator flaps in a rat model

Bioactive nanoparticle-based formulations increase survival area of perforator flaps in a rat model

Transcriptional trajectories of human kidney injury progression

Circulating lectin pathway proteins do not predict short-term cardiac outcomes after myocardial infarction

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