Cartilage Oligomeric Matrix Protein-Angiopoietin-1 Has a Protective Effect of Vascular Endothelial Barrier in Rat With Acute Necrotizing Pancreatitis

Chen, Ya‐Feng; Kong, Pingting; Li, Hongchang; Fan, Xin-Juan; Tu, Jia-min; Xie, Jinkun; Tian, Jianqiu; Pan, Li-yun; Chen, Teng; Cao, Yijun; Yin, Peihao; Peng, Wen; Feng, Dan

doi:10.1097/mpa.0000000000000435

Cited by 3 publications

(3 citation statements)

References 19 publications

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“…These results showed that DCQD could effectively alleviate the capillary leakage and the damage to the endothelial barrier function due to the inflammatory reaction process via regulation of the endothelial barrier-related proteins. The results were consistent with the results of our previous study [9, 26]. …”

Section: Discussionsupporting

confidence: 83%

“…It can also regulate the proliferation of endothelial cells and vascular smooth muscle cells to promote the maturation of blood vessels, which is very important for maintaining the stability and integrity of blood vessels [23-25]. Our previous studies found that serum Ang-1 levels in AP rats are significantly decreased, and after treatment with Ang-1, the amounts of inflammatory factors in serum dramatically decline and the capillary permeability of tissue decreases [26]. Therefore, this experiment used Ang-1 in the positive control group.…”

Section: Discussionmentioning

confidence: 99%

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Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo

Pan

Chen

et al. 2017

Cell Physiol Biochem

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Background/Aims: Dachengqi decoction (DCQD) is a well-known traditional Chinese herbal drug with strong anti-inflammatory effects. Angiopoietin-1 (Ang-1) plays a vital role in maintaining the stability and integrity of the vascular wall and prevents vascular leakage due to inflammatory mediators. Our previous work found that DCQD protects against pancreatic injury in rats with severe acute pancreatitis (SAP). This study aims to investigate the effects of DCQD on intestinal endothelial damage in both damaged human umbilical vein endothelial cells (HUVECs) and SAP rats. Methods: HUVECs were randomly divided into four groups: control group, TNF-α group, TNF-α plus Ang-1 group (Ang-1 group), and TNF-α plus DCQD group (DCQD group). Cells were incubated for 6 h, 12 h, and 24 h, before collection. The treatment concentration of DCQD was decided based on a Cell Counting Kit-8 (CCK-8) assay. The monolayer permeability of the HUVECs was assessed by measuring the transendothelial electrical resistance (TEER). Apoptosis was analyzed by flow cytometry. mRNA and protein expression of aquaporin 1 (AQP-1), matrix metalloproteinase 9 (MMP9), and junctional adhesion molecule-C (JAM-C) was evaluated by RT-PCR, immunocytofluorescence, and western blot. Forty male Sprague-Dawley rats were randomized into a control group, SAP group, SAP plus Ang-1 group (Ang-1 group), and SAP plus DCQD group (DCQD group). SAP was induced by intraperitoneal injection of cerulein and lipopolysaccharide (LPS), while the control group received 0.9% saline solution. Evans blue was injected through the penile vein and the rats were then sacrificed 12 h after modeling. Levels of serum amylase, TNF-α, IL-1β, IL-2, and IL-6 were determined by using ELISA. Intestinal tissue was analysed by histology, and capillary permeability in the tissues was evaluated by Evans blue extravasation assay. Protein and mRNA expression of AQP-1, MMP9, and JAM-C were assessed by immunohistofluorescence, western blot, and RT-PCR. Results: DCQD reduced the permeability of HUVEC induced by TNF-α in vitro. Furthermore, DCQD altered the mRNA and protein levels of JAM-C, MMP9, and AQP-1 in HUVECs after TNF-α induction. SAP intestinal injury induced by cerulein combined with lipopolysaccharides was concomitant with increased expression of JAM-C and MMP9, and reduced expression of AQP-1 in intestinal tissue. Pretreatment with DCQD attenuated SAP intestinal injury and lowered the levels of serum amylase, TNF–α, IL-1β, IL-2, and IL-6 effectively. Our study demonstrated that DCQD decreased the expression of JAM-C and MMP9 and increased the expression of AQP-1 both in vitro and in vivo. Conclusion: DCQD can reduce capillary endothelial damage in acute pancreatitis-associated intestinal injury and the mechanism may be associated with the regulation of endothelial barrier function-associated proteins AQP-1, MMP9, and JAM-C.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo

Pan

Chen

et al. 2017

Cell Physiol Biochem

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“…In support of this hypothesis, a limited number of mainly in vivo studies have previously reported the ability of COMP-Ang1 to improve microvascular function. Cho et al11 showed that COMP-Ang1 can promote wound healing through enhancement of angiogenesis and blood flow in diabetic db/db mice, whereas Chen et al12 demonstrated that COMP-Ang1 can protect endothelial barriers in rats with acute necrotizing pancreatitis. Subretinal and intravitreal delivery of COMP-Ang1 cloned into an adeno-associated virus vector (AAV2.COMP-Ang1) exhibited microvasculature-related improvements in mouse models of AMD13 and diabetic retinopathy,14 respectively.…”

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confidence: 99%

COMP-Ang1 Stabilizes Hyperglycemic Disruption of Blood-Retinal Barrier Phenotype in Human Retinal Microvascular Endothelial Cells

Rochfort

Carroll

Barabás

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Purpose Current treatments for diabetic retinopathy (DR) have considerable limitations, underpinning the need for new therapeutic options. In this article, the ability of an engineered angiopoietin-1 variant (COMP-Ang1) to ameliorate the injurious effects of hyperglycemia on barrier integrity in a human retinal microvascular endothelial cell (HRMvEC) model is comprehensively investigated. Methods Confluent HRMvECs were treated (0–72 hours) with d -glucose (5 or 30 mM) in the absence and presence of COMP-Ang1 (10–200 ng/mL). l -glucose (30 mM) was used as osmotic control. Posttreatment, intact cell monolayers were monitored for permeability to FITC-dextran 40 kDa. Cells were also harvested for analysis of interendothelial junction targets by RT-qPCR and Western blotting. The impact of receptor tyrosine kinase Tie2 gene silencing on COMP-Ang1 efficacy was also evaluated. Results Treatment with 30 mM d -glucose (but not l -glucose) demonstrated a time-dependent elevation in the mean rate of FITC-dextran diffusion across intact HRMvEC monolayers, in parallel with significant reductions in mRNA/protein levels of occludin, claudin-5, ZO-1, and VE-Cadherin. These effects were all attenuated by COMP-Ang1 in a concentration-dependent fashion, with 200 ng/mL recovering barrier function by ∼88%, and recovering reduced interendothelial junction protein levels by more than 50%. Finally, Tie2 knockdown by small interfering RNA silencing blocked the ability of COMP-Ang1 to mitigate against hyperglycemia-induced permeabilization of HRMvECs and depletion of junctional expression levels. Conclusions In summary, this article presents a reproducible in vitro cell study that quantifies the concentration-dependent efficacy of COMP-Ang1 to mitigate the injurious effects of hyperglycemic challenge on HRMvEC barrier properties via Tie2-mediated signaling.

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Overexpression of Angiopoietin-1 Potentiates Endothelial Progenitor Cells for the Treatment of Aneurysm

Wang

Chen

et al. 2018

Annals of Vascular Surgery

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Cartilage Oligomeric Matrix Protein-Angiopoietin-1 Has a Protective Effect of Vascular Endothelial Barrier in Rat With Acute Necrotizing Pancreatitis

Abstract: COMP-Ang-1 can upregulate the expression of Ang-1 protein to promote angiogenesis and improve early inflammatory and pathological damage in ANP group.

Cited by 3 publications

References 19 publications

Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo

Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo

COMP-Ang1 Stabilizes Hyperglycemic Disruption of Blood-Retinal Barrier Phenotype in Human Retinal Microvascular Endothelial Cells

Overexpression of Angiopoietin-1 Potentiates Endothelial Progenitor Cells for the Treatment of Aneurysm

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