Modulation of EndMT by Hydrogen Sulfide in the Prevention of Cardiovascular Fibrosis

Testai, Lara; Brancaleone, Vincenzo; Flori, Lorenzo; Montanaro, Rosangela; Calderone, Vincenzo

doi:10.3390/antiox10060910

Cited by 35 publications

(23 citation statements)

References 178 publications

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“…Also, epigenetic modifications might participate in EndMT and play an important role in cardiovascular diseases. DNA methylation, histone modifications and RNA interference are recognized as the most involved ( 82 ). However, EndMT is a complex process and due to the lack of standardization, relative expression of endothelial versus mesenchymal markers should be graduated and reversible or transient characteristics should be evaluated when one wants to show EndMT ( 87 ).…”

Section: Endothelial Phenotypical Changes: Endothelial-to-mesenchymal...mentioning

confidence: 99%

“…Type I activation results in the activation of the canonical SMAD signaling pathway. Activated SMAD proteins form heterodimeric complexes with SMAD4 and translocate into the nucleus ( 82 ). There, they interact with various transcription factors such as Snail, Twist, Zeb and Slug and regulate the transcription of genes involved in EndMT ( 75 ).…”

Section: Molecular Mechanisms and Regulation Of Endmtmentioning

confidence: 99%

“…Elevated HDL levels show anti-fibrotic effects by blocking the TGFβ/SMAD/Slug/ZEB signaling pathway. On the contrary, high glucose conditions have been shown to induce EndMT through the Akt/PI3K/NFκB pathway ( 82 ). Several studies showed that cytokine combination is more powerful in inducing EndMT.…”

Section: Molecular Mechanisms and Regulation Of Endmtmentioning

confidence: 99%

“…PTEN is a target of miR-21 and an inhibitor of Akt which facilitates EndMT. Several other miRNAs were found to be modulated in EndMT but their precise role has not been defined yet ( 82 , 100 ).…”

Section: Molecular Mechanisms and Regulation Of Endmtmentioning

confidence: 99%

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Endothelial Cell Phenotype, a Major Determinant of Venous Thrombo-Inflammation

Pilard

Gourdou-Latyszenok

Couturaud

et al. 2022

Front. Cardiovasc. Med.

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Reduced blood flow velocity in the vein triggers inflammation and is associated with the release into the extracellular space of alarmins or damage-associated molecular patterns (DAMPs). These molecules include extracellular nucleic acids, extracellular purinergic nucleotides (ATP, ADP), cytokines and extracellular HMGB1. They are recognized as a danger signal by immune cells, platelets and endothelial cells. Hence, endothelial cells are capable of sensing environmental cues through a wide variety of receptors expressed at the plasma membrane. The endothelium is then responding by expressing pro-coagulant proteins, including tissue factor, and inflammatory molecules such as cytokines and chemokines involved in the recruitment and activation of platelets and leukocytes. This ultimately leads to thrombosis, which is an active pro-inflammatory process, tightly regulated, that needs to be properly resolved to avoid further vascular damages. These mechanisms are often dysregulated, which promote fibrinolysis defects, activation of the immune system and irreversible vascular damages further contributing to thrombotic and inflammatory processes. The concept of thrombo-inflammation is now widely used to describe the complex interactions between the coagulation and inflammation in various cardiovascular diseases. In endothelial cells, activating signals converge to multiple intracellular pathways leading to phenotypical changes turning them into inflammatory-like cells. Accumulating evidence suggest that endothelial to mesenchymal transition (EndMT) may be a major mechanism of endothelial dysfunction induced during inflammation and thrombosis. EndMT is a biological process where endothelial cells lose their endothelial characteristics and acquire mesenchymal markers and functions. Endothelial dysfunction might play a central role in orchestrating and amplifying thrombo-inflammation thought induction of EndMT processes. Mechanisms regulating endothelial dysfunction have been only partially uncovered in the context of thrombotic diseases. In the present review, we focus on the importance of the endothelial phenotype and discuss how endothelial plasticity may regulate the interplay between thrombosis and inflammation. We discuss how the endothelial cells are sensing and responding to environmental cues and contribute to thrombo-inflammation with a particular focus on venous thromboembolism (VTE). A better understanding of the precise mechanisms involved and the specific role of endothelial cells is needed to characterize VTE incidence and address the risk of recurrent VTE and its sequelae.

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Section: Endothelial Phenotypical Changes: Endothelial-to-mesenchymal...mentioning

confidence: 99%

Section: Molecular Mechanisms and Regulation Of Endmtmentioning

confidence: 99%

Section: Molecular Mechanisms and Regulation Of Endmtmentioning

confidence: 99%

Section: Molecular Mechanisms and Regulation Of Endmtmentioning

confidence: 99%

See 2 more Smart Citations

Endothelial Cell Phenotype, a Major Determinant of Venous Thrombo-Inflammation

Pilard

Gourdou-Latyszenok

Couturaud

et al. 2022

Front. Cardiovasc. Med.

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“…In DM, patients with insufficient oxygen supplies due to impaired angiogenesis/neovascularization [ 12 ], refractory wounds and critical ischemic sufferance in limbs are major vascular hazards [ 11 ], connected with a malfunction of endothelial cells (ECs) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Molecular Research on Hydrogen Sulfide (H2S) Role in Diabetes Mellitus (DM)—A Systematic Review

Munteanu

Rotariu

Turnea

et al. 2022

IJMS

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Abundant experimental data suggest that hydrogen sulfide (H2S) is related to the pathophysiology of Diabetes Mellitus (DM). Multiple molecular mechanisms, including receptors, membrane ion channels, signalingmolecules, enzymes, and transcription factors, are known to be responsible for the H2S biological actions; however, H2S is not fully documented as a gaseous signaling molecule interfering with DM and vascular-linked pathology. In recent decades, multiple approaches regarding therapeutic exploitation of H2S have been identified, either based on H2S exogenous apport or on its modulated endogenous biosynthesis. This paper aims to synthesize and systematize, as comprehensively as possible, the recent literature-related data regarding the therapeutic/rehabilitative role of H2S in DM. This review was conducted following the “Preferred reporting items for systematic reviews and meta-analyses” (PRISMA) methodology, interrogating five international medically renowned databases by specific keyword combinations/“syntaxes” used contextually, over the last five years (2017–2021). The respective search/filtered and selection methodology we applied has identified, in the first step, 212 articles. After deploying the next specific quest steps, 51 unique published papers qualified for minute analysis resulted. To these bibliographic resources obtained through the PRISMA methodology, in order to have the best available information coverage, we added 86 papers that were freely found by a direct internet search. Finally, we selected for a connected meta-analysis eight relevant reports that included 1237 human subjects elicited from clinical trial registration platforms. Numerous H2S releasing/stimulating compounds have been produced, some being used in experimental models. However, very few of them were further advanced in clinical studies, indicating that the development of H2S as a therapeutic agent is still at the beginning.

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Why is endothelial resilience key to maintain cardiac health?

Tombor

Dimmeler

2022

Basic Res Cardiol

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Myocardial injury as induced by myocardial infarction results in tissue ischemia, which critically incepts cardiomyocyte death. Endothelial cells play a crucial role in restoring oxygen and nutrient supply to the heart. Latest advances in single-cell multi-omics, together with genetic lineage tracing, reveal a transcriptional and phenotypical adaptation to the injured microenvironment, which includes alterations in metabolic, mesenchymal, hematopoietic and pro-inflammatory signatures. The extent of transition in mesenchymal or hematopoietic cell lineages is still debated, but it is clear that several of the adaptive phenotypical changes are transient and endothelial cells revert back to a naïve cell state after resolution of injury responses. This resilience of endothelial cells to acute stress responses is important for preventing chronic dysfunction. Here, we summarize how endothelial cells adjust to injury and how this dynamic response contributes to repair and regeneration. We will highlight intrinsic and microenvironmental factors that contribute to endothelial cell resilience and may be targetable to maintain a functionally active, healthy microcirculation.

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Modulation of EndMT by Hydrogen Sulfide in the Prevention of Cardiovascular Fibrosis

Cited by 35 publications

References 178 publications

Endothelial Cell Phenotype, a Major Determinant of Venous Thrombo-Inflammation

Endothelial Cell Phenotype, a Major Determinant of Venous Thrombo-Inflammation

Recent Advances in Molecular Research on Hydrogen Sulfide (H2S) Role in Diabetes Mellitus (DM)—A Systematic Review

Why is endothelial resilience key to maintain cardiac health?

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