Involvement of miR-30a-5p and miR-30d in Endothelial to Mesenchymal Transition and Early Osteogenic Commitment under Inflammatory Stress in HUVEC

The endothelial to mesenchymal transition (End–MT) can be associated with vascular calcification, by providing mesengenic progenitors. In this study, we investigated a link between End–MT and the osteogenic process and explored the involvement of miR-30a-5p and miR-30d as potential regulators of these processes. End–MT was induced in Human Umbilical Vein Endothelial Cells (HUVEC) through transforming growth factor-β1 (TGF-β1), TGFβ-3 and tumor necrosis factor-α (TNF-α), for 24 h and 6 days. End–MT mediators, mesenchymal and osteo/chondrogenic markers were analyzed through Real-Time PCR, immunofluorescence, flow cytometry and Western Blot. miR-30a-5p and miR-30d over-expression was carried out in HUVEC to explore their effects on End–MT and osteogenic differentiation. HUVEC at 24 h and 6 days gained mesenchymal morphology markers, including matrix metalloproteinase 9 (MMP-9), SLUG, VIMENTIN and α-smooth muscle actin (α-SMA), and a significant migratory potential, notably with TNF-α. After 6 days, the osteo/chondrogenic markers runt-related transcription factor 2 (RUNX-2) and SRY box transcription factor 9 (SOX-9) were upregulated. At this time point, miR-30a-5p and miR-30d decreased. Over-expression of miR-30a-5p and miR-30d affected End–MT mediators and the osteogenic potency in HUVEC, by reducing SLUG, VIMENTIN and RUNX-2. Our data suggest that End–MT represents a key link between inflammation and vascular calcification. Further, miR-30a-5p and miR-30d can regulate both the End–MT and the osteogenic processes, prompting future studies for exploring their potential use as therapeutic targets or biomarkers in vascular diseases.

Download Full-text

Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition

International Journal of Molecular Sciences ◽

10.3390/ijms20030458 ◽

2019 ◽

Vol 20 (3) ◽

pp. 458 ◽

Cited By ~ 9

Author(s):

Fernanda Ursoli Ferreira ◽

Lucas Eduardo Botelho Souza ◽

Carolina Hassibe Thomé ◽

Mariana Tomazini Pinto ◽

Clarice Origassa ◽

...

Keyword(s):

Endothelial Cells ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Umbilical Vein ◽

Transforming Growth Factor Β ◽

Selective Inhibition ◽

Mesenchymal Transition ◽

Best Response ◽

Endothelial To Mesenchymal Transition

The endothelial-to-mesenchymal transition (EndMT) is a biological process where endothelial cells (ECs) acquire a fibroblastic phenotype after concomitant loss of the apical-basal polarity and intercellular junction proteins. This process is critical to embryonic development and is involved in diseases such as fibrosis and tumor progression. The signaling pathway of the transforming growth factor β (TGF-β) is an important molecular route responsible for EndMT activation. However, it is unclear whether the anatomic location of endothelial cells influences the activation of molecular pathways responsible for EndMT induction. Our study investigated the molecular mechanisms and signaling pathways involved in EndMT induced by TGF-β2 in macrovascular ECs obtained from different sources. For this purpose, we used four types of endothelial cells (coronary artery endothelial cells, CAECs; primary aortic endothelial cells PAECs; human umbilical vein endothelia cells, HUVECs; and human pulmonary artery endothelial cells, HPAECs) and stimulated with 10 ng/mL of TGF-β2. We observed that among the ECs analyzed in this study, PAECs showed the best response to the TGF-β2 treatment, displaying phenotypic changes such as loss of endothelial marker and acquisition of mesenchymal markers, which are consistent with the EndMT activation. Moreover, the PAECs phenotypic transition was probably triggered by the extracellular signal–regulated kinases 1/2 (ERK1/2) signaling pathway activation. Therefore, the anatomical origin of ECs influences their ability to undergo EndMT and the selective inhibition of the ERK pathway may suppress or reverse the progression of diseases caused or aggravated by the involvement EndMT activation.

Download Full-text

MALAT1 Modulates TGF-β1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145

Cellular Physiology and Biochemistry ◽

10.1159/000477479 ◽

2017 ◽

Vol 42 (1) ◽

pp. 357-372 ◽

Cited By ~ 67

Author(s):

Yin Xiang ◽

Yachen Zhang ◽

Yong Tang ◽

Qianhui Li

Keyword(s):

Target Genes ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Neointimal Hyperplasia ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Reporter Assay ◽

Mesenchymal Transition ◽

Endothelial To Mesenchymal Transition ◽

Tgf Β1

Background/Aims: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells. In the present study, we investigated the role of MALAT1 and miR-145 in EndMT of human circulating EPCs induced by transforming growth factor beta1 (TGF-β1). Methods: Human circulating EPCs were isolated and characterized by fluorescence-activated cell sorting (FACS). Expression levels of EndMT markers were assessed by qRT-PCR and western blotting. Alpha-smooth muscle actin (α-SMA) expression was measured by cell immunofluorescence staining. The regulatory relationship between MALAT1 and miR-145 and its target genes, TGFBR2 (TGFβ receptortype II) and SMAD3 (mothers against decapentaplegic homolog 3) was analyzed using the luciferase reporter assay. Results: We found that EndMT of EPCs induced by TGF-β1 is accompanied by increased MALAT1 expression and decreased miR-145 expression, and MALAT1 and miR-145 directly bind and reciprocally repress each other in these cells. Dual-Luciferase Reporter assay indicated that miR-145 inhibits TGF-β1-induced EndMT by directly targeting TGFBR2 and SMAD3. Conclusions: MALAT1 modulates TGF-β1-induced EndMT of EPCs through regulation of TGFBR2 and SMAD3 via miR-145. Thus, the MALAT1-miR-145-TGFBR2/SMAD3 signaling pathway plays a key role in TGF-β1-induced EndMT.

Download Full-text

Calcitriol Attenuates Doxorubicin-Induced Cardiac Dysfunction and Inhibits Endothelial-to-Mesenchymal Transition in Mice

Cells ◽

10.3390/cells8080865 ◽

2019 ◽

Vol 8 (8) ◽

pp. 865 ◽

Cited By ~ 5

Author(s):

Tsai ◽

Lin ◽

Hang ◽

Chen

Keyword(s):

Myocardial Fibrosis ◽

Cardiac Fibrosis ◽

Transforming Growth Factor ◽

Cardiac Fibroblasts ◽

Umbilical Vein ◽

Active Form ◽

Mesenchymal Transition ◽

Endothelial To Mesenchymal Transition ◽

Umbilical Vein Endothelial Cells

Doxorubicin (Dox) is an effective anti-neoplasm drug, but its cardiac toxicity limits its clinical use. Endothelial-to-mesenchymal transition (EndMT) has been found to be involved in the process of heart failure. It is unclear whether EndMT contributes to Dox-induced cardiomyopathy (DoIC). Calcitriol, an active form Vitamin D3, blocks the growth of cancer cells by inhibiting the Smad pathway. To investigate the effect of calcitriol via inhibiting EndMT in DoIC, C57BL/6 mice and endothelial-specific labeled mice were intraperitoneally administered Dox twice weekly for 4 weeks (32 mg/kg cumulative dose) and were subsequently treated with or without calcitriol for 12 weeks. Echocardiography revealed diastolic dysfunction at 13 weeks following the first Dox treatment, accompanied by increased myocardial fibrosis and up-regulated pro-fibrotic proteins. Calcitriol attenuated Dox-induced myocardial fibrosis, down-regulated pro-fibrotic proteins and improved diastolic function. Endothelial fate tracing revealed that EndMT-derived cells contributed to Dox-induced cardiac fibrosis. In vitro, human umbilical vein endothelial cells and mouse cardiac fibroblasts were treated with Transforming growth factor (TGF)-β with or without calcitriol. Morphological, immunofluorescence staining, and Western blot analyses revealed that TGF-β-induced EndMT and fibroblast-to-myofibroblast transition (FMT) were attenuated by calcitriol by the inhibition of the Smad2 pathway. Collectively, calcitriol attenuated DoIC through the inhibition of the EndMT and FMT processes.

Download Full-text

TGF-β-Induced Endothelial to Mesenchymal Transition Is Determined by a Balance Between SNAIL and ID Factors

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.616610 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jin Ma ◽

Gerard van der Zon ◽

Manuel A. F. V. Gonçalves ◽

Maarten van Dinther ◽

Midory Thorikay ◽

...

Keyword(s):

Transcription Factor ◽

Transforming Growth Factor ◽

Ectopic Expression ◽

Mesenchymal Cell ◽

Transforming Growth Factor Β ◽

Mesenchymal Transition ◽

Id Proteins ◽

Morphogenetic Protein ◽

Endothelial To Mesenchymal Transition ◽

Inhibitor Of Dna Binding

Endothelial-to-mesenchymal transition (EndMT) plays an important role in embryonic development and disease progression. Yet, how different members of the transforming growth factor-β (TGF-β) family regulate EndMT is not well understood. In the current study, we report that TGF-β2, but not bone morphogenetic protein (BMP)9, triggers EndMT in murine endothelial MS-1 and 2H11 cells. TGF-β2 strongly upregulates the transcription factor SNAIL, and the depletion of Snail is sufficient to abrogate TGF-β2-triggered mesenchymal-like cell morphology acquisition and EndMT-related molecular changes. Although SLUG is not regulated by TGF-β2, knocking out Slug also partly inhibits TGF-β2-induced EndMT in 2H11 cells. Interestingly, in addition to SNAIL and SLUG, BMP9 stimulates inhibitor of DNA binding (ID) proteins. The suppression of Id1, Id2, or Id3 expression facilitated BMP9 in inducing EndMT and, in contrast, ectopic expression of ID1, ID2, or ID3 abrogated TGF-β2-mediated EndMT. Altogether, our results show that SNAIL is critical and indispensable for TGF-β2-mediated EndMT. Although SLUG is also involved in the EndMT process, it plays less of a crucial role in it. In contrast, ID proteins are essential for maintaining endothelial traits and repressing the function of SNAIL and SLUG during the EndMT process. These data suggest that the control over endothelial vs. mesenchymal cell states is determined, at least in part, by a balance between the expression of SNAIL/SLUG and ID proteins.

Download Full-text

Evodiamine Prevents Isoproterenol-Induced Cardiac Fibrosis by Regulating Endothelial-to-Mesenchymal Transition

Planta Medica ◽

10.1055/s-0042-124044 ◽

2016 ◽

Vol 83 (09) ◽

pp. 761-769 ◽

Cited By ~ 13

Author(s):

Xiao-han Jiang ◽

Qing-qing Wu ◽

Yang Xiao ◽

Yuan Yuan ◽

Zheng Yang ◽

...

Keyword(s):

Smooth Muscle ◽

Cardiac Fibrosis ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Transforming Growth Factor Β1 ◽

Heart Weight ◽

Muscle Actin ◽

Mesenchymal Transition ◽

Expression Levels ◽

Endothelial To Mesenchymal Transition

AbstractEvodiamine, a major component of Evodia rutaecarpa, can protect the myocardium against injury induced by atherosclerosis and ischemia-reperfusion. However, the effect of evodiamine against cardiac fibrosis remains unclear. This study aims to investigate the possible effect and mechanism involved in the function of evodiamine on isoproterenol-induced cardiac fibrosis and endothelial-to-mesenchymal transition. Isoproterenol was used to induce cardiac fibrosis in mice, and evodiamine was gavaged simultaneously. After 14 days, cardiac function was accessed by echocardiography. The extent of cardiac fibrosis and hypertrophy was evaluated by pathological and molecular analyses. The extent of endothelial-to-mesenchymal transition was evaluated by the expression levels of CD31, CD34, α-smooth muscle actin, and vimentin by immunofluorescence staining and Western blot analysis. After 14 days, the heart weight/body weight ratio and heart weight/tibia length ratio revealed no significant difference between the isoproterenol group and the isoproterenol/evodiamine-treated groups, whereas the increased heart weight was reduced in the isoproterenol/evodiamine-treated groups. Echocardiography revealed that interventricular septal thickness and left ventricular posterior wall thickness at the end diastole decreased in the evodiamine-treated groups. Evodiamine reduced isoproterenol-induced cardiac fibrosis as accessed by normalization in collagen deposition and gene expression of hypertrophic and fibrotic markers. Evodiamine also prevented endothelial-to-mesenchymal transition as evidenced by the increased expression levels of CD31 and CD34, decreased expression levels of α-smooth muscle actin and vimentin, and increased microvascular density in the isoproterenol/evodiamine-treated mice hearts. Furthermore, isoproterenol-induced activation of transforming growth factor-β1/Smad signal was also blunted by evodiamine. Therefore, evodiamine may prevent isoproterenol-induced cardiac fibrosis by regulating endothelial-to-mesenchymal transition, which is probably mediated by the blockage of the transforming growth factor-β1/Smad pathway.

Download Full-text

KLF2 Mediates the Suppressive Effect of Laminar Flow on Vascular Calcification by Inhibiting Endothelial BMP/SMAD1/5 Signaling

Circulation Research ◽

10.1161/circresaha.120.318690 ◽

2021 ◽

Author(s):

Juan Huang ◽

Yujie Pu ◽

Hongsong Zhang ◽

Liping Xie ◽

Lei He ◽

...

Keyword(s):

Blood Flow ◽

Laminar Flow ◽

Vascular Calcification ◽

Umbilical Vein ◽

Suppressive Effect ◽

Aortic Valves ◽

Mesenchymal Transition ◽

Arterial Intima ◽

Endothelial To Mesenchymal Transition ◽

Underlying Mechanisms

Rationale: Vascular calcification in arterial intima is closely associated with atherosclerosis. Endothelial cells (ECs) sense blood flow and respond to the mechanical cues generated by different flow patterns. Laminar flow (LF) induces an anti-atherosclerotic EC phenotype whereas disturbed flow (DF) exerts an atheroprone effect. However, the contribution of blood flow to calcification in atherosclerotic arteries remains to be evaluated. Objective: We aim to investigate whether blood flow plays a determinant role in the distribution of vascular calcification and the underlying mechanisms involved. Methods and Results: Computed tomography angiography analysis of human coronary arteries (n = 48) shows that calcification preferentially develops at flow perturbated sites. Similar phenomenon was observed in calcified human aortic valves and mouse arteries. Nonuniform shear stress produced in Y-shaped slide simulating live conditions in branched arteries promotes calcification in human umbilical vein ECs (HUVECs). The expression of Krüppel-like Factor 2 (KLF2), a transcription factor inducible by LF, is reduced in ECs of calcified human aortic valves and in endothelial calcification model, suggesting that KLF2 downregulation is likely involved in intimal calcification. Indeed, KLF2 silencing induces endothelial-to-mesenchymal transition and accelerates osteo-induction in both human aortic ECs and HUVECs. EC-specific KLF2 knockdown promotes whereas AAV9-mediated EC-KLF2 overexpression ameliorates vascular calcification in ApoE -/- mice. Global mRNA profiling in HUVECs reveals that KLF2 inhibits BMP/SMAD1/5 pathway which is critical in vascular calcification. Furthermore, KLF2 mediates LF-induced inhibition of the BMP/SMAD1/5 pathway. By contrast, DF-induced activation of BMP/SMAD1/5 pathway is suppressed by KLF2 overexpression. Mechanistically, KLF2 binds to the promoters of BMP4, BMPER and SMAD1 to directly regulate their expression in ECs. Conclusions: Vascular calcification prefers to occur at branched or bifurcated areas of vasculature. LF inhibits vascular calcification through KLF2-mediated inhibition of endothelial BMP/SMAD1/5 signaling. Targeting KLF2 may represent a novel therapeutic approach against vascular calcification.

Download Full-text

MiR-126-3p Is Dynamically Regulated in Endothelial-to-Mesenchymal Transition during Fibrosis

International Journal of Molecular Sciences ◽

10.3390/ijms22168629 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8629

Author(s):

Nina P. Jordan ◽

Samuel J. Tingle ◽

Victoria G. Shuttleworth ◽

Katie Cooke ◽

Rachael E. Redgrave ◽

...

Keyword(s):

Endothelial Cells ◽

Umbilical Vein ◽

Cell Types ◽

Heart Tissue ◽

Lineage Tracing ◽

Ischaemic Injury ◽

Kidney Fibrosis ◽

Mesenchymal Transition ◽

Over Expression ◽

Endothelial To Mesenchymal Transition

In fibrotic diseases, myofibroblasts derive from a range of cell types including endothelial-to-mesenchymal transition (EndMT). Increasing evidence suggests that miRNAs are key regulators in biological processes but their profile is relatively understudied in EndMT. In human umbilical vein endothelial cells (HUVEC), EndMT was induced by treatment with TGFβ2 and IL1β. A significant decrease in endothelial markers such as VE-cadherin, CD31 and an increase in mesenchymal markers such as fibronectin were observed. In parallel, miRNA profiling showed that miR-126-3p was down-regulated in HUVECs undergoing EndMT and over-expression of miR-126-3p prevented EndMT, maintaining CD31 and repressing fibronectin expression. EndMT was investigated using lineage tracing with transgenic Cdh5-Cre-ERT2; Rosa26R-stop-YFP mice in two established models of fibrosis: cardiac ischaemic injury and kidney ureteric occlusion. In both cardiac and kidney fibrosis, lineage tracing showed a significant subpopulation of endothelial-derived cells expressed mesenchymal markers, indicating they had undergone EndMT. In addition, miR-126-3p was restricted to endothelial cells and down-regulated in murine fibrotic kidney and heart tissue. These findings were confirmed in patient kidney biopsies. MiR-126-3p expression is restricted to endothelial cells and is down-regulated during EndMT. Over-expression of miR-126-3p reduces EndMT, therefore, it could be considered for miRNA-based therapeutics in fibrotic organs.

Download Full-text

Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia

Rheumatology ◽

10.1093/rheumatology/kez159 ◽

2019 ◽

Vol 58 (11) ◽

pp. 1966-1975 ◽

Cited By ~ 2

Author(s):

Chaofan Liu ◽

Xing Zhou ◽

Jinghao Lu ◽

Lubing Zhu ◽

Ming Li

Keyword(s):

Collagen Synthesis ◽

Umbilical Vein ◽

Smooth Muscle Actin ◽

Tissue Growth ◽

Collagen I ◽

Bafilomycin A1 ◽

Mesenchymal Transition ◽

Transmission Electron ◽

Endothelial To Mesenchymal Transition ◽

Umbilical Vein Endothelial Cells

Abstract Objectives To investigate whether autophagy mediates 2-methoxyestradiol (2-ME)-inhibited hypoxia-induced fibrosis and endothelial-to-mesenchymal transition (endoMT) in SSc. Methods Autophagy in the skin of SSc patients was assessed by transmission electron microscopy. SSc skin fibroblasts and human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic (1% O2) conditions with 2-ME or autophagy inhibitor. Collagen I and connective tissue growth factor (CTGF) in fibroblasts and vascular endothelial (VE)-cadherin, CD31, vimentin and α-smooth muscle actin (α-SMA) in HUVECs were examined by western blotting. Autophagic markers were evaluated by confocal microscopy and immunofluorescence. Results SSc skins presented increased autolysosomes, LC3-II, collagen I and CTGF. Hypoxia-challenged fibroblasts and HUVECs formed more autophagosomes and autolysosomes, with increased LC3 and decreased P62. Meanwhile, hypoxia increased collagen I and CTGF in fibroblasts and increased vimentin and α-SMA but decreased VE-cadherin and CD31 in HUVECs. Bafilomycin A1 increased LC3-II and P62 in fibroblasts and HUVECs and decreased collagen I and CTGF in fibroblasts and vimentin and α-SMA in HUVECs, while upregulating VE-cadherin and CD31. 3-methyladenine decreased autophagy and fibrosis in fibroblasts and endothelial-to-mesenchymal transition in HUVECs. 2-ME-treated HUVECs showed more autophagosomes and fewer autolysosomes while 2-ME-treated fibroblasts showed fewer of both. Moreover, 2-ME decreased LC3-II and increased P62 in fibroblasts and increased both in HUVECs. Inhibition of autophagy by 2-ME showed the same effect with bafilomycin A1 on fibroblast collagen synthesis as well as endothelial and mesenchymal markers in HUVECs. Conclusion Autophagy mediated hypoxia-induced fibroblast collagen synthesis and endoMT in SSc, which could be reversed by 2-ME.

Download Full-text

Naringin Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension Through Endothelial-To-Mesenchymal Transition Inhibition

Frontiers in Pharmacology ◽

10.3389/fphar.2021.696135 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yonghui Wu ◽

Changhong Cai ◽

Yijia Xiang ◽

Huan Zhao ◽

Lingchun Lv ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Signaling Pathways ◽

Transforming Growth Factor ◽

Umbilical Vein ◽

Pulmonary Arteries ◽

Mesenchymal Transition ◽

Pulmonary Arterial ◽

Marker Expression ◽

Endothelial To Mesenchymal Transition

Pulmonary arterial hypertension (PAH) caused by enhanced arterial pressure increases vessel resistance in the lung. Endothelial-to-mesenchymal transition (EndMT) plays key roles in the vascular remodeling in PAH. Naringin, a protective gaseous mediator is commonly extracted from tomatoes and citrus fruits (such as grapefruits), and demonstrates anti-inflammation, anti-oxidant, anti-proliferation, and anti-tumor effects. Meanwhile, the association of Naringin and the process of EndMT is still unclear. In this study, monocrotaline (MCT) administration (60 mg/kg) was delivered for the induction of PAH in rats. Following this, Naringin (concentrations: 25, 50, and 100 mg/kg/day) was used for treatments. Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with Naringin and transforming growth factor β1 (TGFβ1, 10 ng/ml). As the result, Naringin was demonstrated to inhibit EndMT and alleviate PAH progression. In particular, in HUVECs, Naringin significantly suppressed the mesenchymal marker expression induced by TGFβ1 treatment, enhanced the endothelial marker expression, and inhibited the activation of ERK and NF-κB signaling pathways. To conclude, this study provided novel evidence suggesting the beneficial effects of Naringin in PAH through the inhibition of the ERK and NF-κB signaling pathways and the EndMT progression in pulmonary arteries.

Download Full-text

Mechanistic studies on the role of TGF-β1 in angiogenesis through EndMT

Vascular ◽

10.1177/1708538120953668 ◽

2020 ◽

pp. 170853812095366

Author(s):

Sheng-Jun Cao ◽

Lei Hong ◽

Xiao-Qiang Li

Keyword(s):

Growth Factor ◽

Transforming Growth Factor ◽

Umbilical Vein ◽

Transforming Growth Factor Β1 ◽

Tube Formation ◽

Mesenchymal Transition ◽

Phosphorylated Akt ◽

Endothelial To Mesenchymal Transition ◽

Umbilical Vein Endothelial Cells ◽

Tgf Β1

Objective This study aims to investigate the mechanism of transforming growth factor-β1 (TGF-β1) in promoting angiogenesis through endothelial-to-mesenchymal transition (EndMT). Methods The mesenchymal transition of human umbilical vein endothelial cells (HUVECs) was induced by TGF-β1. The angiogenesis, migration, and proliferation of HUVECs undergoing EndMT were examined by tube formation assay, scratch assay, Transwell assay, and CCK-8 assay. Results The outcomes revealed that EndMT promoted angiogenesis, migration, and proliferation of HUVECs and the secretion of the vascular endothelial growth factor (VEGF) of HUVECs. Phosphorylated AKT (p-AKT) increased in EndMT by inhibiting the mitigation of angiogenesis. Conclusion EndMT induces angiogenesis by promoting the secretion of VEGF, and p-AKT participates in this regulation.

Download Full-text