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.

scholarly journals Cytoskeleton Reorganization in EndMT—The Role in Cancer and Fibrotic Diseases

2021 ◽  
Vol 22 (21) ◽  
pp. 11607
Author(s):  
Wojciech Michał Ciszewski ◽  
Marta Ewelina Wawro ◽  
Izabela Sacewicz-Hofman ◽  
Katarzyna Sobierajska
Keyword(s):  
Cell Shape ◽  
Current Knowledge ◽  
Cell Junctions ◽  
Migration And Invasion ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Cytoskeleton Reorganization ◽  
Fibrotic Diseases ◽  
Endothelial Plasticity ◽  
Endothelial Mesenchymal Transition

Chronic inflammation promotes endothelial plasticity, leading to the development of several diseases, including fibrosis and cancer in numerous organs. The basis of those processes is a phenomenon called the endothelial–mesenchymal transition (EndMT), which results in the delamination of tightly connected endothelial cells that acquire a mesenchymal phenotype. EndMT-derived cells, known as the myofibroblasts or cancer-associated fibroblasts (CAFs), are characterized by the loss of cell–cell junctions, loss of endothelial markers, and gain in mesenchymal ones. As a result, the endothelium ceases its primary ability to maintain patent and functional capillaries and induce new blood vessels. At the same time, it acquires the migration and invasion potential typical of mesenchymal cells. The observed modulation of cell shape, increasedcell movement, and invasion abilities are connected with cytoskeleton reorganization. This paper focuses on the review of current knowledge about the molecular pathways involved in the modulation of each cytoskeleton element (microfilaments, microtubule, and intermediate filaments) during EndMT and their role as the potential targets for cancer and fibrosis treatment.

scholarly journals LncRNA AERRIE Is Required for Sulfatase 1 Expression, but Not for Endothelial-to-Mesenchymal Transition

2021 ◽  
Vol 22 (15) ◽  
pp. 8088
Author(s):  
Tan Phát Pham ◽  
Anke S. van Bergen ◽  
Veerle Kremer ◽  
Simone F. Glaser ◽  
Stefanie Dimmeler ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Transcription Factors ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Inflammatory Signals ◽  
Pathological Conditions ◽  
Non Coding Rna ◽  
Endothelial To Mesenchymal Transition ◽  
Long Non Coding Rna

Endothelial cells can acquire a mesenchymal phenotype through a process called Endothelial-to-Mesenchymal transition (EndMT). This event is found in embryonic development, but also in pathological conditions. Blood vessels lose their ability to maintain vascular homeostasis and ultimately develop atherosclerosis, pulmonary hypertension, or fibrosis. An increase in inflammatory signals causes an upregulation of EndMT transcription factors, mesenchymal markers, and a decrease in endothelial markers. In our study, we show that the induction of EndMT results in an increase in long non-coding RNA AERRIE expression. JMJD2B, a known EndMT regulator, induces AERRIE and subsequently SULF1. Silencing of AERRIE shows a partial regulation of SULF1 but showed no effect on the endothelial and mesenchymal markers. Additionally, the overexpression of AERRIE results in no significant changes in EndMT markers, suggesting that AERRIE is marginally regulating mesenchymal markers and transcription factors. This study identifies AERRIE as a novel factor in EndMT, but its mechanism of action still needs to be elucidated.

scholarly journals Involvement of Extracellular Vesicles in Vascular-Related Functions in Cancer Progression and Metastasis

2019 ◽  
Vol 20 (10) ◽  
pp. 2584 ◽  
Author(s):  
Shinsuke Kikuchi ◽  
Yusuke Yoshioka ◽  
Marta Prieto-Vila ◽  
Takahiro Ochiya
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Cell Communication ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Patients With Cancer ◽  
Tumor Environment ◽  
Endothelial To Mesenchymal Transition

The primary cause of mortality among patients with cancer is the progression of the tumor, better known as cancer invasion and metastasis. Cancer progression involves a series of biologically important steps in which the cross-talk between cancer cells and the cells in the surrounding environment is positioned as an important issue. Notably, angiogenesis is a key tumorigenic phenomenon for cancer progression. Cancer-related extracellular vesicles (EVs) commonly contribute to the modulation of a microenvironment favorable to cancer cells through their function of cell-to-cell communication. Vascular-related cells such as endothelial cells (ECs) and platelets activated by cancer cells and cancer-derived EVs develop procoagulant and proinflammatory statuses, which help excite the tumor environment, and play major roles in tumor progression, including in tumor extravasation, tumor cell microthrombi formation, platelet aggregation, and metastasis. In particular, cancer-derived EVs influence ECs, which then play multiple roles such as contributing to tumor angiogenesis, loss of endothelial vascular barrier by binding to ECs, and the subsequent endothelial-to-mesenchymal transition, i.e., extracellular matrix remodeling. Thus, cell-to-cell communication between cancer cells and ECs via EVs may be an important target for controlling cancer progression. This review describes the current knowledge regarding the involvement of EVs, especially exosomes derived from cancer cells, in EC-related cancer progression.

scholarly journals Extracellular Vesicles Are Key Regulators of Tumor Neovasculature

2020 ◽  
Vol 8 ◽  
Author(s):  
Naoya Kuriyama ◽  
Yusuke Yoshioka ◽  
Shinsuke Kikuchi ◽  
Nobuyoshi Azuma ◽  
Takahiro Ochiya
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Tumor Angiogenesis ◽  
Current Knowledge ◽  
Cell Communication ◽  
Multiple Roles ◽  
Mesenchymal Transition ◽  
Surrounding Environment ◽  
Endothelial To Mesenchymal Transition ◽  
Review Current

Tumor progression involves a series of biologically important steps in which the crosstalk between cancer cells and the surrounding environment is an important issue. Angiogenesis is a key tumorigenic phenomenon for cancer progression. Tumor-related extracellular vesicles (EVs) modulate the tumor microenvironment (TME) through cell-to-cell communication. Tumor cells in a hypoxic TME release more EVs than cells in a normoxic environment due to uncontrollable tumor proliferation. Tumor-derived EVs in the TME influence endothelial cells (ECs), which then play multiple roles, contributing to tumor angiogenesis, loss of the endothelial vascular barrier by binding to ECs, and subsequent endothelial-to-mesenchymal transition. In contrast, they also indirectly induce tumor angiogenesis through the phenotype switching of various cells into cancer-associated fibroblasts, the activation of tumor-associated ECs and platelets, and remodeling of the extracellular matrix. Here, we review current knowledge regarding the involvement of EVs in tumor vascular-related cancer progression.

scholarly journals The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition

2020 ◽  
Vol 117 (8) ◽  
pp. 4180-4187 ◽  
Author(s):  
Simone F. Glaser ◽  
Andreas W. Heumüller ◽  
Lukas Tombor ◽  
Patrick Hofmann ◽  
Marion Muhly-Reinholz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular System ◽  
Histone Demethylase ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Hypoxic Conditions ◽  
Endothelial To Mesenchymal Transition ◽  
And Function ◽  
A Site

Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under proinflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional properties of endothelial cells. Here, we investigated the epigenetic control of EndMT. We show that the histone demethylase JMJD2B is induced by EndMT-promoting, proinflammatory, and hypoxic conditions. Silencing of JMJD2B reduced TGF-β2-induced expression of mesenchymal genes, prevented the alterations in endothelial morphology and impaired endothelial barrier function. Endothelial-specific deletion of JMJD2B in vivo confirmed a reduction of EndMT after myocardial infarction. EndMT did not affect global H3K9me3 levels but induced a site-specific reduction of repressive H3K9me3 marks at promoters of mesenchymal genes, such as Calponin (CNN1), and genes involved in TGF-β signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and Sulfatase 1 (SULF1). Silencing of JMJD2B prevented the EndMT-induced reduction of H3K9me3 marks at these promotors and further repressed these EndMT-related genes. Our study reveals that endothelial identity and function is critically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting, proinflammatory, and hypoxic conditions, and supports the acquirement of a mesenchymal phenotype.

scholarly journals Endothelial-Mesenchymal Transition or Functional Tissue Regeneration – Two Outcomes of Heart Remodeling

2021 ◽  
pp. S13-S20
Author(s):  
B. Šalingová ◽  
Z. Červenák ◽  
A. Adamičková ◽  
N. Chomanicová ◽  
S. Valášková ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Current Knowledge ◽  
Cardiac Fibroblasts ◽  
Scar Tissue ◽  
Mesenchymal Transition ◽  
Heart Remodeling ◽  
Circulating Endothelial Progenitor Cells ◽  
Heart Repair ◽  
Endothelial Mesenchymal Transition

Heart remodeling occurs as a compensation mechanism for the massive loss of tissue during initial heart failure and the consequent inflammation process. During heart remodeling fibroblasts differentiate to myofibroblasts activate their secretion functions and produce elevated amounts, of extracellular matrix (ECM) proteins, mostly collagen, that form scar tissue and alter the normal degradation of ECM. Scar formation does replace the damaged tissue structurally; however, it impedes the normal contractive function of cardiomyocytes (CMs) and results in long-lasting effects after heart failure. Besides CMs and cardiac fibroblasts, endothelial cells (ECs) and circulating endothelial progenitor cells (cEPCs) contribute to heart repair. This review summarizes the current knowledge of EC-CM crosstalk in cardiac fibrosis (CF), the role of cEPCs in heart regeneration and the contribution of Endothelial-mesenchymal transition (EndoMT).

scholarly journals N-acetyl-seryl-aspartyl-lysyl-proline Inhibits Diabetes-Associated Kidney Fibrosis and Endothelial-Mesenchymal Transition

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Takako Nagai ◽  
Megumi Kanasaki ◽  
Swayam Prakash Srivastava ◽  
Yuka Nakamura ◽  
Yasuhito Ishigaki ◽  
...  
Keyword(s):  
Ace Inhibitor ◽  
Receptor Expression ◽  
Fgf Receptor ◽  
Diabetic Kidney ◽  
Kidney Fibrosis ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

Endothelial-to-mesenchymal transition (EndMT) emerges as an important source of fibroblasts. MicroRNA let-7 exhibits anti-EndMT effects and fibroblast growth factor (FGF) receptor has been shown to be an important in microRNA let-7 expression. The endogenous antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a substrate of angiotensin-converting enzyme (ACE). Here, we found that AcSDKP inhibited the EndMT and exhibited fibrotic effects that were associated with FGF receptor-mediated anti-fibrotic program. Conventional ACE inhibitor plus AcSDKP ameliorated kidney fibrosis and inhibited EndMT compared to therapy with the ACE inhibitor alone in diabetic CD-1 mice. The endogenous AcSDKP levels were suppressed in diabetic animals. Cytokines induced cultured endothelial cells into EndMT; coincubation with AcSDKP inhibited EndMT. Expression of microRNA let-7 family was suppressed in the diabetic kidney; antifibrotic and anti-EndMT effects of AcSDKP were associated with the restoration of microRNA let-7 levels. AcSDKP restored diabetes- or cytokines-suppressed FGF receptor expression/phosphorylation into normal levels both in vivo and in vitro. These results suggest that AcSDKP is an endogenous antifibrotic molecule that has the potential to cure diabetic kidney fibrosis via an inhibition of the EndMT associated with the restoration of FGF receptor and microRNA let-7.

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