scholarly journals Endothelial to Mesenchymal Transition: An Insight in Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Qingyan Huang ◽  
Yuhong Gan ◽  
Zhikang Yu ◽  
Heming Wu ◽  
Zhixiong Zhong
Keyword(s):  
Molecular Mechanisms ◽  
Plaque Formation ◽  
The Other ◽  
High Morbidity ◽  
Endothelial Cell Dysfunction ◽  
Mesenchymal Transition ◽  
Substantial Body ◽  
Cell Dysfunction ◽  
Endothelial To Mesenchymal Transition ◽  
The One

Atherosclerosis is a fundamental disease of the cardiovascular system that leads to high morbidity and mortality worldwide. The endothelium is the first protective barrier in atherosclerosis. Endothelial cells have the potential to be transformed into mesenchymal cells, in a process termed endothelial to mesenchymal transition (EndMT). On the one hand, EndMT is known to contribute to atherosclerosis by inducing a number of phenotypes ranging from endothelial cell dysfunction to plaque formation. On the other hand, risk factors for atherosclerosis can lead to EndMT. A substantial body of evidence has suggested that EndMT induces the development of atherosclerosis; therefore, a deeper understanding of the molecular mechanisms underlying EndMT in atherosclerosis might provide insights to reverse this condition.

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

2019 ◽  
Vol 20 (3) ◽  
pp. 458 ◽  
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.

Genetic Engineering of Disease and Pest Resistance in Plants: Present State of the Art

1993 ◽  
Vol 48 (9-10) ◽  
pp. 673-688 ◽  
Author(s):  
Günter Strittmatter ◽  
Dorothee Wegener
Keyword(s):  
Host Plants ◽  
Molecular Mechanisms ◽  
State Of The Art ◽  
Durable Resistance ◽  
The Other ◽  
Rapid Progress ◽  
Pathogenic Viruses ◽  
The One ◽  
Defence Strategies ◽  
Defence Reactions

Abstract Rapid progress in gene technology has allowed, on the one hand, insight to be gained into the complex molecular mechanisms of plant/pathogen recognition and the natural defence strategies of host plants. On the other hand, this technology can also be used for the controlled and efficient generation of genetic variability and for the identification of desirable genotypes, far beyond the possibilities of classical breeding. The first successful attempts have been made to improve resistance against pathogenic viruses, bacteria, fungi and insects by engineering transgenic plants. The majority of these strategies were based on constitutively expressing single proteins that are either toxic to the pathogen/pest, or interfere with its reproductive cycle. More refined strategies, which are at the stage of testing, try to mimic and modify naturally-evolved defence reactions of plants and, thereby, will potentially confer a more durable resistance to a broad range of pathogens

scholarly journals MIR503HG Loss Promotes Endothelial-to-Mesenchymal Transition in Vascular Disease

2021 ◽  
Author(s):  
João P. Monteiro ◽  
Julie Rodor ◽  
Axelle Caudrillier ◽  
Jessica P Scanlon ◽  
Ana-Mishel Spiroski ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Molecular Mechanisms ◽  
Clinical Samples ◽  
Vascular Remodelling ◽  
Mesenchymal Transition ◽  
Polypyrimidine Tract Binding Protein ◽  
Endothelial To Mesenchymal Transition

Rationale: Endothelial-to-mesenchymal transition (EndMT) is a dynamic biological process involved in pathological vascular remodelling. However, the molecular mechanisms that govern this transition remain largely unknown, including the contribution of long non-coding RNAs (lncRNAs). Objective: To investigate the role of lncRNAs in EndMT and their relevance to vascular remodelling. Methods and Results: To study EndMT in vitro, primary endothelial cells (EC) were treated with transforming growth factor-β2 and interleukin-1β. Single-cell and bulk RNA-sequencing were performed to investigate the transcriptional architecture of EndMT and identify regulated lncRNAs. The functional contribution of seven lncRNAs during EndMT was investigated based on a DsiRNA screening assay. The loss of lncRNA MIR503HG was identified as a common signature across multiple human EC types undergoing EndMT in vitro. MIR503HG depletion induced a spontaneous EndMT phenotype, while its overexpression repressed hallmark EndMT changes, regulating 29% of its transcriptome signature. Importantly, the phenotypic changes induced by MIR503HG were independent of miR-424 and miR-503, which overlap the lncRNA locus. The pathological relevance of MIR503HG down-regulation was confirmed in vivo using Sugen/Hypoxia (SuHx)-induced pulmonary hypertension (PH) in mouse, as well as in human clinical samples, in lung sections and blood outgrowth endothelial cells (BOECs) from pulmonary arterial hypertension (PAH) patients. Overexpression of human MIR503HG in SuHx mice led to reduced mesenchymal marker expression, suggesting MIR503HG therapeutic potential. We also revealed that MIR503HG interacts with the Polypyrimidine Tract Binding Protein 1 (PTB1) and regulates its protein level. PTBP1 regulation of EndMT markers suggests that the role of MIR503HG in EndMT might be mediated in part by PTBP1. Conclusions: This study reports a novel lncRNA transcriptional profile associated with EndMT and reveals the crucial role of the loss of MIR503HG in EndMT and its relevance to pulmonary hypertension.

Souster, Raymond (1921–2012)

2018 ◽  
Author(s):  
Conrad Scott
Keyword(s):  
Human Condition ◽  
The Other ◽  
Substantial Body ◽  
Founding Member ◽  
The World ◽  
The One ◽  
The City ◽  
Modern Era ◽  
The Human Condition

Raymond Holmes Souster has been described as a poet of place who invests Toronto, the city of his life-long residence, deeply into his writing. Having worked for some forty-five years at the downtown Canadian Imperial Bank of Commerce, Souster’s immersion in a particular place certainly informed his poetic output; however, Souster the poet also ponders the human condition. On the one hand, he writes from a basis of experience: the destruction of war and the changes imposed by the rise of the modern era. On the other, his work seeks out and highlights that which is still precious despite the weight of the world he feels. Moreover, he clearly values poetry as a salve to the cacophonous imposition of modernity, and continually encourages poetic development: in addition to his substantial body of work, he has supported Canadian poetry by editing several anthologies, and as a creator of Direction (editor 1943–6); a founder of Contact (editor 1952–4); an editor of Combustion (1957–60); and a founding member of the League of Canadian Poets (president 1967–71).

scholarly journals The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-21 ◽  
Author(s):  
Ya-Dan Wen ◽  
Hong Wang ◽  
Yi-Zhun Zhu
Keyword(s):  
Cardiovascular Disease ◽  
Hydrogen Sulfide ◽  
Molecular Mechanisms ◽  
Pathological Process ◽  
The Other ◽  
Acid Oxidase ◽  
Organosulfur Compounds ◽  
Amino Acid Oxidase ◽  
Mercaptopyruvate Sulfurtransferase ◽  
The One

The recognition of hydrogen sulfide (H2S) has been evolved from a toxic gas to a physiological mediator, exhibiting properties similar to NO and CO. On the one hand, H2S is produced from L-cysteine by enzymes of cystathionineγ-lyase (CSE) and cystathionineβ-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST) in combination with aspartate aminotransferase (AAT) (also called as cysteine aminotransferase, CAT); on the other hand, H2S is produced from D-cysteine by enzymes of D-amino acid oxidase (DAO). Besides sulfide salt, several sulfide-releasing compounds have been synthesized, including organosulfur compounds, Lawesson’s reagent and analogs, and plant-derived natural products. Based on garlic extractions, we synthesized S-propargyl-L-cysteine (SPRC) and its analogs to contribute our endeavors on drug development of sulfide-containing compounds. A multitude of evidences has presented H2S is widely involved in the roles of physiological and pathological process, including hypertension, atherosclerosis, angiogenesis, and myocardial infarcts. This review summarizes current sulfide compounds, available H2S measurements, and potential molecular mechanisms involved in cardioprotections to help researchers develop further applications and therapeutically drugs.

scholarly journals Angioregulatory microRNAs in Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 71 ◽  
Author(s):  
Mohammad Hasan Soheilifar ◽  
Michael Grusch ◽  
Hoda Keshmiri Neghab ◽  
Razieh Amini ◽  
Hamid Maadi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
The Other ◽  
Angiogenic Response ◽  
Rate Determining Step ◽  
Antiangiogenic Factors ◽  
The One ◽  
Tumor Suppressor Mirnas

Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Angiogenesis is a rate-determining step in CRC development and metastasis. The balance of angiogenic and antiangiogenic factors is crucial in this process. Angiogenesis-related genes can be regulated post-transcriptionally by microRNAs (miRNAs) and some miRNAs have been shown to shuttle between tumor cells and the tumor microenvironment (TME). MiRNAs have context-dependent actions and can promote or suppress angiogenesis dependent on the type of cancer. On the one hand, miRNAs downregulate anti-angiogenic targets and lead to angiogenesis induction. Tumor suppressor miRNAs, on the other hand, enhance anti-angiogenic response by targeting pro-angiogenic factors. Understanding the interaction between these miRNAs and their target mRNAs will help to unravel molecular mechanisms involved in CRC progression. The aim of this article is to review the current literature on angioregulatory miRNAs in CRC.

scholarly journals Lipid-Induced Mechanisms of Metabolic Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Yulia K. Denisenko ◽  
Oxana Yu Kytikova ◽  
Tatyana P. Novgorodtseva ◽  
Marina V. Antonyuk ◽  
Tatyana A. Gvozdenko ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Insulin Response ◽  
The Body ◽  
Diagnostic Methods ◽  
The Other ◽  
Prevention And Treatment ◽  
The One

Metabolic syndrome (MetS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnosis, approaches to the prevention, and treatment of this pathology. Insulin resistance (IR) is the crucial cause of the MetS pathogenesis, which develops against the background of abdominal obesity. In light of recent evidence, it has been shown that lipids, especially fatty acids (FAs), are important signaling molecules that regulate the signaling pathways of insulin and inflammatory mediators. On the one hand, the lack of n-3 polyunsaturated fatty acids (PUFAs) in the body leads to impaired molecular mechanisms of glucose transport, the formation of unresolved inflammation. On the other hand, excessive formation of free fatty acids (FFAs) underlies the development of oxidative stress and mitochondrial dysfunction in MetS. Understanding the molecular mechanisms of the participation of FAs and their metabolites in the pathogenesis of MetS will contribute to the development of new diagnostic methods and targeted therapy for this disease. The purpose of this review is to highlight recent advances in the study of the effect of fatty acids as modulators of insulin response and inflammatory process in the pathogenesis and treatment for MetS.

Endothelial cell dysfunction: can’t live with it, how to live without it

2005 ◽  
Vol 288 (5) ◽  
pp. F871-F880 ◽  
Author(s):  
Michael S. Goligorsky
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Asymmetric Dimethylarginine ◽  
Cardiovascular Complications ◽  
Therapeutic Strategies ◽  
Renal Diseases ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction ◽  
Definition Of

Endothelial cell dysfunction is emerging as an ultimate culprit for diverse cardiovascular diseases and cardiovascular complications of chronic renal diseases, yet the definition of this new syndrome, its pathophysiology, and therapy remain poorly defined. Here, I summarize some molecular mechanisms leading from hyperhomocystinemia, elevated asymmetric dimethylarginine, and advanced glycolation end product-modified protein level to the proatherogenic, prothrombogenic, and proinflammatory endothelial phenotype and offer a model of endothelial dysfunction based on the interconnectedness of diverse functions. Finally, several therapeutic strategies to prevent and correct endothelial dysfunction are discussed in the light of uncertainty of their action modulated by the endothelial dysfunction per se.

scholarly journals Breast Cancer and the Other Non-Coding RNAs

2021 ◽  
Vol 22 (6) ◽  
pp. 3280
Author(s):  
Dana Dvorská ◽  
Dušan Braný ◽  
Marcela Ňachajová ◽  
Erika Halašová ◽  
Zuzana Danková
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Breast Cancer Cell Lines ◽  
Altered Expression ◽  
Factors Affecting ◽  
Mesenchymal Transition ◽  
Non Coding Rnas ◽  
Endothelial To Mesenchymal Transition ◽  
Molecular Therapeutic

Breast cancer is very heterogenous and the most common gynaecological cancer, with various factors affecting its development. While its impact on human lives and national health budgets is still rising in almost all global areas, many molecular mechanisms affecting its onset and development remain unclear. Conventional treatments still prove inadequate in some aspects, and appropriate molecular therapeutic targets are required for improved outcomes. Recent scientific interest has therefore focused on the non-coding RNAs roles in tumour development and their potential as therapeutic targets. These RNAs comprise the majority of the human transcript and their broad action mechanisms range from gene silencing to chromatin remodelling. Many non-coding RNAs also have altered expression in breast cancer cell lines and tissues, and this is often connected with increased proliferation, a degraded extracellular environment, and higher endothelial to mesenchymal transition. Herein, we summarise the known abnormalities in the function and expression of long non-coding RNAs, Piwi interacting RNAs, small nucleolar RNAs and small nuclear RNAs in breast cancer, and how these abnormalities affect the development of this deadly disease. Finally, the use of RNA interference to suppress breast cancer growth is summarised.

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