Endothelial mechanobiology in atherosclerosis

Cardiovascular Research, Journal Year: 2023, Volume and Issue: 119(8), P. 1656 - 1675

Published: May 10, 2023

Abstract Cardiovascular disease (CVD) is a serious health challenge, causing more deaths worldwide than cancer. The vascular endothelium, which forms the inner lining of blood vessels, plays central role in maintaining integrity and homeostasis direct contact with flow. Research over past century has shown that mechanical perturbations wall contribute to formation progression atherosclerosis. While straight part artery exposed sustained laminar flow physiological high shear stress, near branch points or curved vessels can exhibit ‘disturbed’ Clinical studies as well carefully controlled vitro analyses have confirmed these regions disturbed flow, include low recirculation, oscillation, lateral are preferential sites atherosclerotic lesion formation. Because their critical homeostasis, endothelial cells (ECs) mechanosensory mechanisms allow them react rapidly changes forces, execute context-specific adaptive responses modulate EC functions. This review summarizes current understanding mechanobiology, guide identification new therapeutic targets slow reverse

Language: Английский

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Acetate controls endothelial-to-mesenchymal transition

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(7), P. 1163 - 1178.e10

Published: June 15, 2023

Language: Английский

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Endothelial dysfunction in vascular complications of diabetes: a comprehensive review of mechanisms and implications

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: April 5, 2024

Diabetic vascular complications are prevalent and severe among diabetic patients, profoundly affecting both their quality of life long-term prospects. These can be classified into macrovascular microvascular complications. Under the impact risk factors such as elevated blood glucose, pressure, cholesterol lipids, endothelium undergoes endothelial dysfunction, characterized by increased inflammation oxidative stress, decreased NO biosynthesis, endothelial-mesenchymal transition, senescence, even cell death. processes will ultimately lead to diseases, with diseases mainly atherosclerosis (AS) thickening basement membrane. It further indicates a primary contributor morbidity mortality observed in individuals diabetes. In this review, we delve intricate mechanisms that drive dysfunction during diabetes progression its associated Furthermore, outline various pharmacotherapies targeting hope accelerating effective therapeutic drug discovery for early control

Language: Английский

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Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease

Cardiovascular Research, Journal Year: 2024, Volume and Issue: 120(3), P. 223 - 236

Published: Feb. 1, 2024

Abstract Endothelial cells (ECs) line the luminal surface of blood vessels and play a major role in vascular (patho)-physiology by acting as barrier, sensing circulating factors intrinsic/extrinsic signals. ECs have capacity to undergo endothelial-to-mesenchymal transition (EndMT), complex differentiation process with key roles both during embryonic development adulthood. EndMT can contribute EC activation dysfunctional alterations associated maladaptive tissue responses human disease. During EndMT, progressively changes leading expression mesenchymal markers while repressing lineage-specific traits. This phenotypic functional switch is considered largely exist continuum, being characterized gradation transitioning stages. In this report, we discuss plasticity potential reversibility hypothesis that different EndMT-derived cell populations may disease progression or resolution. addition, review advancements field, current technical challenges, well therapeutic options opportunities context cardiovascular biology.

Language: Английский

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Vascular remodelling in cardiovascular diseases: hypertension, oxidation, and inflammation

Clinical Science, Journal Year: 2024, Volume and Issue: 138(13), P. 817 - 850

Published: June 26, 2024

Abstract Optimal vascular structure and function are essential for maintaining the physiological functions of cardiovascular system. Vascular remodelling involves changes in vessel structure, including its size, shape, cellular molecular composition. These result from multiple risk factors may be compensatory adaptations to sustain blood function. They occur diverse pathologies, hypertension heart failure atherosclerosis. Dynamic endothelium, fibroblasts, smooth muscle cells, pericytes or other wall cells underlie remodelling. In addition, immune macrophages lymphocytes, infiltrate vessels initiate inflammatory signalling. contribute a dynamic interplay between cell proliferation, apoptosis, migration, inflammation, extracellular matrix reorganisation, all critical mechanisms Molecular pathways underlying these processes include growth (e.g., endothelial factor platelet-derived factor), cytokines interleukin-1β tumour necrosis factor-α), reactive oxygen species, signalling pathways, such as Rho/ROCK, MAPK, TGF-β/Smad, related nitric oxide superoxide biology. MicroRNAs long noncoding RNAs crucial epigenetic regulators gene expression We evaluate potential therapeutic targeting clinical translational perspective. summary, remodelling, coordinated modification function, is disease pathology.

Language: Английский

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Endothelial cells in tumor microenvironment: insights and perspectives

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 15, 2024

The tumor microenvironment is a highly complex and dynamic mixture of cell types, including tumor, immune endothelial cells (ECs), soluble factors (cytokines, chemokines, growth factors), blood vessels extracellular matrix. Within this network, ECs are not only relevant for controlling fluidity permeability, orchestrating angiogenesis but also regulating the antitumor response. Lining luminal side vessels, check passage molecules into compartment, regulate cellular transmigration, interact with both circulating pathogens innate adaptive cells. Thus, they represent first-line defense system that participates in responses. Tumor-associated involved T priming, activation, proliferation by acting as semi-professional antigen presenting targeting may assist improving functions. Moreover, tumor-associated contribute to development at site tertiary lymphoid structures, which have recently been associated enhanced response checkpoint inhibitors (ICI). When compared normal ECs, abnormal terms phenotype, genetic expression profile, They characterized high proliferative potential ability activate immunosuppressive mechanisms support progression metastatic dissemination. A complete phenotypic functional characterization could be helpful clarify their role within identify EC specific drug targets improve cancer therapy. emerging therapeutic strategies based on combination anti-angiogenic treatments immunotherapy strategies, ICI, CAR bispecific antibodies aim impact block same time increase recruitment activation effector tumor.

Language: Английский

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ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(7), P. 3027 - 3048

Published: March 12, 2024

Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis increased in the endothelium atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated lactate, can regulate gene expression and participate disease regulation. However, whether histone lactylation involved atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced increasing lactate-dependent H3 lysine 18 (H3K18la) vitro vivo, as well atherosclerotic patients' arteries. Mechanistically, chaperone ASF1A was first identified cofactor P300, which precisely regulated enrichment H3K18la at promoter SNAI1, thereby activating SNAI1 transcription promoting EndMT. We found deletion inhibited EndMT improved endothelial dysfunction. Functional analysis based on ApoeKOAsf1aECKO mice model confirmed involvement endothelium-specific deficiency alleviated development. Inhibition pharmacologic inhibition advanced PROTAC attenuated H3K18la, transcription, This study illustrates precise crosstalk between metabolism epigenetics via P300/ASF1A molecular complex during atherogenesis, provides emerging therapies for

Language: Английский

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Probiotics in Wound Healing

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5723 - 5723

Published: May 24, 2024

Wound infections caused by opportunistic bacteria promote persistent infection and represent the main cause of delayed healing. Probiotics are acknowledged for their beneficial effects on human body could be utilized in management various diseases. They also possess capacity to accelerate wound healing, due remarkable anti-pathogenic, antibiofilm, immunomodulatory effects. Oral topical probiotic formulations have shown promising openings field dermatology, there vitro vivo models focusing healing mechanisms. dressings embedded with prebiotics probiotics now prime candidates designing therapeutic approaches combat process. The aim this review is conduct an extensive scientific literature regarding efficacy oral management, as well potential dressing embedding pre- stimulating

Language: Английский

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DNMT1-mediated lncRNA MEG3 methylation accelerates endothelial-mesenchymal transition in diabetic retinopathy through the PI3K/Akt/mTOR signaling pathway

AJP Endocrinology and Metabolism, Journal Year: 2020, Volume and Issue: 320(3), P. E598 - E608

Published: Dec. 7, 2020

Diabetic retinopathy (DR) is one of the serious complications that occurs in diabetic patients frequently causes blindness. Long noncoding RNAs (lncRNAs) have been associated with DR pathology. This study aimed to determine underlying mechanism lncRNA maternally expressed gene 3 (MEG3) association DNA methyltransferase 1 (DNMT1) endothelial-mesenchymal transition (endMT) DR. A rat model was induced by streptozotocin (STZ) injection, and a high-glucose (HG)-induced cell established exposing microvascular endothelial cells obtained from retina rats HG. Subsequently, MEG3 overexpressed models characterize its impact on endMT involvement phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target rapamycin (mTOR) signaling pathway. Furthermore, methylation level promoter region determined application methylation-specific polymerase chain reaction, followed chromatin immunoprecipitation assay for enrichment. Finally, we examined regulation DNMT1 HG-induced model. The results revealed downregulated expression models. Overexpressed shown suppress through inhibition PI3K/Akt/mTOR Notably, could promote inhibit recruiting methyltransferase, which activated pathway accelerate These findings further highlighted inhibitory effect DR, thus presenting novel therapeutic candidate treatment.

Language: Английский

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Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension

Antioxidants and Redox Signaling, Journal Year: 2020, Volume and Issue: 34(12), P. 891 - 914

Published: Aug. 4, 2020

Endothelial-to-mesenchymal transition (EndMT) is a process that encompasses extensive transcriptional reprogramming of activated endothelial cells leading to shift toward mesenchymal cellular phenotypes and functional responses. Initially observed in the context embryonic development, last few decades EndMT increasingly recognized as contributes variety pathologies adult organism. Within settings cardiovascular biology, plays role various diseases, including atherosclerosis, heart valvular disease, cardiac fibrosis, myocardial infarction. also being progressively implicated development progression pulmonary hypertension (PH) arterial (PAH). This review covers current knowledge about PH PAH, provides comprehensive overview seminal discoveries. Topics covered include evidence linking factors associated with PAH hypoxia responses, inflammation, dysregulation bone-morphogenetic protein receptor 2 (BMPR2), redox signaling. amalgamates these discoveries into potential insights for identification underlying mechanisms driving discusses future directions EndMT-based therapeutic strategies disease management.

Language: Английский

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