Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 20, 2023

Abstract Hypertension is a global public health issue and the leading cause of premature death in humans. Despite more than century research, hypertension remains difficult to cure due its complex mechanisms involving multiple interactive factors our limited understanding it. condition that named after clinical features. Vascular function factor affects blood pressure directly, it main strategy for clinically controlling BP regulate constriction/relaxation vessels. elasticity, caliber, reactivity are all characteristic indicators reflecting vascular function. Blood vessels composed three distinct layers, out which endothelial cells intima smooth muscle media performers The alterations signaling pathways these key molecular underlying dysfunction development. In this manuscript, we will comprehensively review involved regulation progression, including calcium pathway, NO-NOsGC-cGMP various remodeling some important upstream such as renin-angiotensin-aldosterone system, oxidative stress-related immunity/inflammation etc. Meanwhile, also summarize treatment methods targets discuss possibility being applied work.

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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Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The modification of endothelial cells (ECs) biological function under pathogenic conditions leads to the expression mesenchymal stromal (MSCs) markers, defined as endothelial-to-mesenchymal transition (EndMT). Invisible in onset and slow progression, atherosclerosis (AS) is a potential contributor various atherosclerotic cardiovascular diseases (ASCVD). By triggering AS, EndMT, "initiator" induces progression ASCVD such coronary heart disease (CHD) ischemic cerebrovascular (ICD), with serious clinical complications myocardial infarction (MI) stroke. In-depth research pathomechanisms EndMT identification targeted therapeutic strategies hold considerable value for prevention treatment ASCVD-associated delayed EndMT. Although previous studies have progressively unraveled complexity its pathogenicity triggered by alterations vascular microenvironmental factors, systematic descriptions most recent roles strategies, their future directions are scarce.

Language: Английский

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Translational opportunities of single-cell biology in atherosclerosis

European Heart Journal, Journal Year: 2022, Volume and Issue: 44(14), P. 1216 - 1230

Published: Dec. 7, 2022

Abstract The advent of single-cell biology opens a new chapter for understanding human biological processes and diagnosing, monitoring, treating disease. This revolution now reaches the field cardiovascular disease (CVD). New technologies to interrogate CVD samples at resolution are allowing identification novel cell communities that important in shaping development direct towards therapeutic strategies. These approaches have begun revolutionize atherosclerosis pathology redraw our development. review discusses state-of-the-art analysis atherosclerotic plaques, with particular focus on lesions, presents current cellular subpopulations their heterogeneity plasticity relation clinically relevant features. Opportunities pitfalls as well clinical impact patient care highlighted, advocating multidisciplinary international collaborative efforts join dots CVD.

Language: Английский

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Epithelial Mesenchymal Transition (EMT) and Associated Invasive Adhesions in Solid and Haematological Tumours

Cells, Journal Year: 2022, Volume and Issue: 11(4), P. 649 - 649

Published: Feb. 13, 2022

In solid tumours, cancer cells that undergo epithelial mesenchymal transition (EMT) express characteristic gene expression signatures promote invasive migration as well the development of stemness, immunosuppression and drug/radiotherapy resistance, contributing to formation currently untreatable metastatic tumours. The traits associated with EMT can be controlled by signalling nodes at adhesion sites (focal contacts, invadopodia microtentacles) where regulation cell migration, cycle progression pro-survival converge. haematological ample evidence accumulated during last decade indicates an EMT-like phenotype is indicative poor disease prognosis. However, this has not been directly linked assembly specific forms adhesions. current review we discuss role in malignancies examine its possible link towards more aggressive these We also known types adhesions formed speculate on their connection phenotype. postulate understanding architecture EMT-related will lead discovery new therapeutic interventions overcome resistance therapies.

Language: Английский

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The multifaceted actions of the lncRNA H19 in cardiovascular biology and diseases

Clinical Science, Journal Year: 2022, Volume and Issue: 136(15), P. 1157 - 1178

Published: Aug. 1, 2022

Abstract Cardiovascular diseases are the leading cause of death and debility worldwide. Various molecular mechanisms have been studied to better understand development progression cardiovascular pathologies with hope eradicate these diseases. With advancement sequencing technology, it is revealed that majority our genome non-coding. A growing body literature demonstrates critical role long non-coding RNAs (lncRNAs) as epigenetic regulators gene expression. LncRNAs can regulate cellular biological processes through various distinct mechanisms. The abundance lncRNAs in system indicates their significance physiology pathology. LncRNA H19, particular, a highly evolutionarily conserved lncRNA enriched cardiac vascular tissue, underlining its importance maintaining homeostasis system. In this review, we discuss versatile function H19 types We highlight current on demonstrate how dysregulation induces pathophysiology.

Language: Английский

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

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: April 21, 2022

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

Language: Английский

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Molecular Determinants of Chronic Venous Disease: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1928 - 1928

Published: Jan. 18, 2023

Chronic Venous Disease (CVD) refers to several pathological and hemodynamic alterations of the veins lower limbs causing a wide range symptoms signs with high prevalence in general population disabling consequences most severe forms. The etiology pathophysiology CVD is complex multifactorial, involving genetic, proteomic, cellular mechanisms that result changes venous structure functions. Expressions genes associated angiogenesis, vascular development, regulation are responsible for susceptibility CVD. Current evidence shows extracellular matrix (ECM) could be identified some cases pharmacologically targeted. This review up date information on molecular determinants order provide complete overview current knowledge this topic. In particular, article explores genetic influence, hormonal ECM imbalance, histopathology role endothelial dysfunction

Language: Английский

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N-Cadherin Targeted Melanin Nanoparticles Reverse the Endothelial–Mesenchymal Transition in Vascular Endothelial Cells to Potentially Slow the Progression of Atherosclerosis and Cancer

ACS Nano, Journal Year: 2024, Volume and Issue: 18(11), P. 8229 - 8247

Published: March 1, 2024

Endothelial–mesenchymal transition (EndoMT) of vascular endothelial cells has recently been considered as a key player in the early progression variety and nonvascular diseases, including atherosclerosis, cancer, organ fibrosis. However, current strategies attempting to identify pharmacological inhibitors block regulatory pathways EndoMT suffer from poor selectivity, unwanted side effects, heterogeneous response with different origins. Furthermore, focus on preventing EndoMT, leaving that have already undergone unresolved. Here, we report design simple but powerful nanoparticle system (i.e., N-cadherin targeted melanin nanoparticles) convert cytokine-activated, mesenchymal-like back their original phenotype. We term this process "Reversed EndoMT" (R-EndoMT). R-EndoMT allows impaired barriers recover quiescence intactness, significantly reduced leukocyte cancer cell adhesion transmigration, which could potentially stop atheromatous plaque formation metastasis stages. is achieved types originating arteries, veins, capillaries, independent activating cytokines. reveal nanoparticles reverse by downregulating an dependent RhoA activation pathway. Overall, approach offers prospect treat multiple EndoMT-associated diseases designing phenotypical cells.

Language: Английский

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Microenvironmental determinants of endothelial cell heterogeneity

Nature Reviews Molecular Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

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