Endothelial-Mesenchymal Transition Occurs during Embryonic Pulmonary Artery Development

Endothelium ◽  
2005 ◽  
Vol 12 (4) ◽  
pp. 193-200 ◽  
Author(s):  
Enrique Arciniegas ◽  
Carmen Yudith Neves ◽  
Luz Marina Carrillo ◽  
Edgar A. Zambrano ◽  
Richard Ramírez
Keyword(s):  
Pulmonary Artery ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

scholarly journals Hypoxia Upregulates NOTCH3 Signaling Pathway to Promote Endothelial-Mesenchymal Transition in Pulmonary Artery Endothelial Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Li-Le Wang ◽  
Xiao-Li Zhu ◽  
Shu-Hua Han ◽  
Lu Xu
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Pulmonary Disease ◽  
Specific Inhibitor ◽  
Specific Marker ◽  
Clinical Prognosis ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Mesenchymal Transformation ◽  
Endothelial Mesenchymal Transition

Background. To investigate the effect of hypoxia on pulmonary artery endothelial cells and the role of NOTCH3 in endothelial-mesenchymal transition (EnMT) and to provide a research model for pulmonary disease and explain the pathogenesis of the pulmonary disease. Methods. Pulmonary artery endothelial cells were divided into two groups and cultured in normoxic and hypoxic environments, respectively. QPCR, western blot, and immunofluorescence were used to detect endothelial cell-specific marker protein and mRNA expression in each group, and the ability of endothelial cells migration was evaluated by scratch and transwell experiment. Results. The pulmonary artery endothelial cells in the normoxic group presented a typical pebble-like arrangement, and the endothelial cells in hypoxic culture showed a long spindle appearance. Hypoxia induced high expression of NOTCH3, Jagged-1, Hes1, c-Src, and CSL. Immunofluorescence showed that endothelial cells in hypoxic culture began to express the α-SMA, and the expression of vWF increased with hypoxia. Cell viability, scratch, and transwell results showed that endothelial cells in the hypoxic group were more capable of viability and migration than those in the normoxic group. The induction of EnMT by hypoxia can be inhibited by using notch3-specific inhibitor DAPT and Jagged-1. This study also found that miR-7-5p can regulate endothelial NOTCH3, indicating that miRNA is also involved in the process of endothelial-mesenchymal transformation. Conclusion. Hypoxia promotes the transformation of endothelial cells into mesenchymal cells by opening the NOTCH3 pathway, which lays the foundation for disease progression or clinical prognosis, and is of great significance in the treatment of diseases.

scholarly journals The Contribution of Endothelial-Mesenchymal Transition to Atherosclerosis

2021 ◽  
Vol 1 (1) ◽  
pp. 39-54
Author(s):  
Jinyu Zhang ◽  
Stella C. Ogbu ◽  
Phillip R. Musich ◽  
Douglas P. Thewke ◽  
Zhiqiang Yao ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Vascular Inflammation ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Common Chronic Disease ◽  
Complex Process ◽  
Endothelial To Mesenchymal Transition ◽  
Key Pathways ◽  
Endothelial Mesenchymal Transition ◽  
Progression Of Atherosclerosis

Atherosclerosis is a chronic progressive condition in which the wall of the artery develops abnormalities and causes thickening of the blood vessels. The development of atherosclerosis is a complex process characterized by vascular inflammation and the growth of atherosclerotic plaques that eventually lead to compromised blood flow. The endothelial to mesenchymal transition (EndMT) is a phenomenon whereby endothelial cells lose their endothelial properties and acquire a mesenchymal phenotype similar to myofibroblast and smooth muscle cells. This process is considered a key contributor to the development and, importantly, the progression of atherosclerosis. Thus, therapeutically targeting the EndMT will provide a broad strategy to attenuate the development of atherosclerosis. Here, we review our current knowledge of EndMT in atherosclerosis including several key pathways such as hypoxia, TGF-β signaling, inflammation, and environmental factors during the development of atherosclerosis. In addition, we discuss several transgenic mouse models for studying atherosclerosis. Taken together, rapidly accelerating knowledge and continued studies promise further progress in preventing this common chronic disease.

Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension

2007 ◽  
Vol 293 (1) ◽  
pp. L1-L8 ◽  
Author(s):  
Enrique Arciniegas ◽  
Maria G. Frid ◽  
Ivor S. Douglas ◽  
Kurt R. Stenmark
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Serine Proteases ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Pulmonary Arteries ◽  
Potential Contribution ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

All forms of pulmonary hypertension are characterized by structural changes in pulmonary arteries. Increased numbers of cells expressing α-smooth muscle (α-SM) actin is a nearly universal finding in the remodeled artery. Traditionally, it was assumed that resident smooth muscle cells were the exclusive source of these newly appearing α-SM actin-expressing cells. However, rapidly emerging experimental evidence suggests other, alternative cellular sources of these cells. One possibility is that endothelial cells can transition into mesenchymal cells expressing α-SM actin and that this process contributes to the accumulation of SM-like cells in vascular pathologies. We review the evidence that endothelial-mesenchymal transition is an important contributor to cardiac and vascular development as well as to pathophysiological vascular remodeling. Recent work has provided evidence for the role of transforming growth factor-β, Wnt, and Notch signaling in this process. The potential roles of matrix metalloproteinases and serine proteases are also discussed. Importantly, endothelial-mesenchymal transition may be reversible. Thus insights into the mechanisms controlling endothelial-mesenchymal transition are relevant to vascular remodeling and are important as we consider new therapies aimed at reversing pulmonary vascular remodeling.

scholarly journals Anti-Fibrosis Effect of Scutellarin via Inhibition of Endothelial–Mesenchymal Transition on Isoprenaline-Induced Myocardial Fibrosis in Rats

Molecules ◽  
2014 ◽  
Vol 19 (10) ◽  
pp. 15611-15623 ◽  
Author(s):  
Hao Zhou ◽  
Xiao Chen ◽  
Lingzhi Chen ◽  
Xi Zhou ◽  
Gaoshu Zheng ◽  
...  
Keyword(s):  
Myocardial Fibrosis ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

Abstract 17763: Inhibition of Bone Morphogenetic Protein Signaling Reduces Endothelial-Mesenchymal Transition and Vascular Smooth Muscle Cell Calcification Associated with Matrix Gla Protein Deficiency

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Megan F Burke ◽  
Caitlin O’Rourke ◽  
Trejeeve Martyn ◽  
Hannah R Shakartzi ◽  
Timothy E Thayer ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Bone Morphogenetic Protein ◽  
Vascular Calcification ◽  
Bmp Signaling ◽  
Matrix Gla Protein ◽  
Wild Type ◽  
Mesenchymal Transition ◽  
Morphogenetic Protein ◽  
Endothelial Mesenchymal Transition

Background: Matrix Gla protein (MGP) is an extracellular matrix protein that inhibits bone morphogenetic protein (BMP) signaling in vitro. MGP deficiency induces vascular calcification associated with osteogenic transdifferentiation of endothelial cells (via endothelial-mesenchymal transition, EndMT) and vascular smooth muscle cells (VSMCs). We previously reported that treatment with two pharmacologic inhibitors of BMP signaling reduced aortic calcification in MGP-/- mice. We hypothesized that BMP signaling is essential for EndMT and VSMC osteogenic transdifferentiation induced by MGP deficiency. Methods and Results: Aortic levels of mRNAs encoding markers of osteogenesis (Runx2 and osteopontin) and EndMT (nanog, Sox2, and Oct3/4) were greater in MGP-/- than in wild-type mice (P<0.01 for all). Aortic expression of markers of VSMC differentiation (α-smooth muscle actin, transgelin, and calponin) was less in MGP-/- than in wild-type mice (P<0.001 for all). Treatment of MGP-/- mice with the BMP signaling inhibitor, LDN-193189, reduced expression of both osteogenic and EndMT markers (P<0.05 for all) but did not prevent VSMC de-differentiation. Depletion of MGP in cultured wild-type VSMCs with siRNA specific for MGP (siMGP) was associated with a 30-40% reduction in levels of mRNAs encoding markers of VSMC differentiation (P<0.05 for all), an effect that was not prevented by LDN-193189. Incubation in phosphate-containing media induced greater calcification in siMGP-treated VSMCs than in cells treated with control siRNA (P<0.0001). Treatment with LDN-193189 reduced calcification in siMGP-treated VSMCs (50%, P=0.0003). Conversely, infection of MGP-/- VSMCs with adenovirus specifying MGP increased expression of markers of VSMC differentiation by 60-80% (P<0.01 for all) and decreased calcification by 74% (P=0.03). Conclusions: Inhibition of BMP signaling suppresses osteogenic and EndMT gene programs in MGP-/- mice and reduces calcification of siMGP-treated VSMCs. However, MGP deficiency induces VSMC de-differentiation via a BMP-independent mechanism. These findings suggest that the processes underlying vascular calcification in MGP deficiency are mediated by both BMP signaling-dependent and -independent mechanisms.

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