Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells

Yi, K.W.; Jung, Su Woong; Cho, G.J.; Seol, Hyun Joo; Hong, Soon Cheol; Oh, Min Jeong; Kim, H.J.

doi:10.1016/j.placenta.2013.09.008

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…We exogenously added α2M to cells after conducting a scratch assay to determine its effect on cell migration. Using different doses of α2M [ 58 ] it was revealed that the high dose of 1000 ng/ml had the greatest effect on cell migration into the scratch zone while the lower doses did not affect cell migration. It is likely that exosomes containing an abundant amount of α2M in their cargo are engulfed by cells in the wound area which enhances cell migration.…”

Section: Discussionmentioning

confidence: 99%

Exosomes from acellular Wharton’s jelly of the human umbilical cord promotes skin wound healing

et al. 2018

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BackgroundCompromised wound healing has become a global public health challenge which presents a significant psychological, financial, and emotional burden on patients and physicians. We recently reported that acellular gelatinous Wharton’s jelly of the human umbilical cord enhances skin wound healing in vitro and in vivo in a murine model; however, the key player in the jelly which enhances wound healing is still unknown.MethodsWe performed mass spectrometry on acellular gelatinous Wharton’s jelly to elucidate the chemical structures of the molecules. Using an ultracentrifugation protocol, we isolated exosomes and treated fibroblasts with these exosomes to assess their proliferation and migration. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or vehicle containing exosomes. Isolated exosomes were subjected to further mass spectrometry analysis to determine their cargo.ResultsSubjecting the acellular gelatinous Wharton’s jelly to proteomics approaches, we detected a large amount of proteins that are characteristic of exosomes. Here, we show that the exosomes isolated from the acellular gelatinous Wharton’s jelly enhance cell viability and cell migration in vitro and enhance skin wound healing in the punch biopsy wound model in mice. Mass spectrometry analysis revealed that exosomes of Wharton’s jelly umbilical cord contain a large amount of alpha-2-macroglobulin, a protein which mimics the effect of acellular gelatinous Wharton’s jelly exosomes on wound healing.ConclusionsExosomes are being enriched in the native niche of the umbilical cord and can enhance wound healing in vivo through their cargo. Exosomes from the acellular gelatinous Wharton’s jelly and the cargo protein alpha-2-macroglobulin have tremendous potential as a noncellular, off-the-shelf therapeutic modality for wound healing.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0921-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Exosomes from acellular Wharton’s jelly of the human umbilical cord promotes skin wound healing

et al. 2018

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“…Although individual maternal plasma/serum markers have not usually performed well as a screening test for preeclampsia [50] , [51] , [53] – [69] and fetal growth restriction [52] , [57] , [58] , combined screening tests to assess the risk of preeclampsia are currently used in practice [66] . In a proposed new approach to prenatal care, screening by a combination of maternal risk factors, mean arterial pressure, uterine artery Doppler and maternal serum biomarkers (pregnancy-associated plasma protein-A and placental growth factor) can identify about 95% of cases with early onset of preeclampsia for a false-positive rate of 10% [66] .…”

Section: Discussionmentioning

confidence: 99%

First Trimester Screening of Circulating C19MC microRNAs Can Predict Subsequent Onset of Gestational Hypertension

et al. 2014

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ObjectiveThe objective of the study was to evaluate risk assessment for gestational hypertension based on the profile of circulating placental specific C19MC microRNAs in early pregnancy.Study designThe prospective longitudinal cohort study of women enrolled at first trimester screening at 10 to 13 weeks was carried out (n = 267). Relative quantification of placental specific C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) was determined in 28 normal pregnancies and 18 pregnancies which developed gestational hypertension using real-time PCR and a comparative Ct method relative to synthetic C. elegans microRNA (cel-miR-39).ResultsIncreased extracellular C19MC microRNA plasmatic levels (miR-516-5p, p<0.001; miR-517*, p = 0.007; miR-520h, p<0.001; miR-518b, p = 0.002) were detected in patients destined to develop gestational hypertension. MiR-520h had the best predictive performance with a PPV of 84.6% at a 7.1% false positive rate. The combination of miR-520h and miR-518b was able to predict 82.6% of women at the same false positive rate. The overall predictive capacity of single miR-518b (73.3% at 14.3% FPR), miR-516-5p (70.6% at 17.9% FPR) and miR-517* (57.9% at 28.6% FPR) biomarkers was lower.ConclusionThe study brought interesting finding that the up-regulation of miR-516-5p, miR-517*, miR-520h and miR-518b is associated with a risk of later development of gestational hypertension. First trimester screening of extracellular miR-520h alone or in combination with miR-518b identified a significant proportion of women with subsequent gestational hypertension.

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“…The α2‐macroglobulin modulates blood coagulation. As reported, α2‐macroglobulin significantly enhanced plasmin generation. However, α2‐macroglobulin binds vascular endothelial growth factor and the resultant α2‐macroglobulin complex inhibits heparin activity, leading to elevated coagulation.…”

Section: Discussionmentioning

confidence: 67%

Relationship of α2‐Macroglobulin with Steroid‐Induced Femoral Head Necrosis: A Chinese Population‐Based Association Study in Southeast China

Fang

Jiang³

et al. 2019

Orthopaedic Surgery

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Objective The present study aimed to identify the relationship of α‐2‐macroglobulin and microvascular vessel pathology with steroid‐induced femoral head necrosis in the Southeast Chinese population. Methods This study enrolled 40 patients diagnosed with steroid‐induced necrosis of the femoral head. Patients had various stages of femoral head necrosis. The differential expression of serum proteins and mRNA from patients with steroid‐induced necrosis of the femoral head (SINFH) and healthy volunteers was analyzed by western blot and quantitative polymerase chain reaction (QT‐PCR). The pathological change in osteocyte necrosis was indicated by hematoxylin and eosin stain and immunohistochemistry. Results Hematoxylin and eosin stain showed histopathology changes in the necrotic area of patients with steroid‐induced INFH: bone trabeculae were fewer and thinner, became broken, fragmented and structurally disordered; intraosseous adipose cells became enlarged; the arrangement of the osteoblasts became irregular; and vacant bone lacunae increased. QT‐PCR showed significantly lower levels of α‐2‐macroglobulin in the serum of patients with SINFH than in controls (P < 0.05). Immunohistochemical staining and western blotting demonstrated that the expression of α‐2‐macroglobulin was significantly decreased in the necrotic area of SINFH patients (P < 0.05). Conclusion The α‐2‐macroglobulin may be associated with the pathology of SINFH. The multiple pathological reactions occur in SINFH and α‐2‐macroglobulin may serve as a potential biomarker for the diagnosis of SINFH or a promising therapeutic target.

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Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells

Cited by 5 publications

References 33 publications

Exosomes from acellular Wharton’s jelly of the human umbilical cord promotes skin wound healing

Exosomes from acellular Wharton’s jelly of the human umbilical cord promotes skin wound healing

First Trimester Screening of Circulating C19MC microRNAs Can Predict Subsequent Onset of Gestational Hypertension

Relationship of α2‐Macroglobulin with Steroid‐Induced Femoral Head Necrosis: A Chinese Population‐Based Association Study in Southeast China

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