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Contribution of Endothelial Dysfunction to Neurovascular and Cardiovascular Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 5579

Special Issue Editor


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Guest Editor
1. Department of Neurosurgery, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany
2. Department of Neurosurgery, University Hospital Helsinki, Topeliuksenkatu 5, 00260 Helsinki, Finland
Interests: intracranial aneurysm; arteriovenous malformation; subarachnoid hemorrhage; endothelial dysfunction; inflammation; senescence; inflammaging
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Special Issue Information

Dear Colleagues,

Endothelial cells line the inner layer of all blood vessels. These are the first cell type in vessels, which come in contact with all kinds of noxious stimuli, including hypertension, hemodynamic shear stress, increased alcohol levels, and the constituents of smoking in blood, resulting in endothelial cell activation, dysfunction, and senescence. The activated endothelial cells increase the expression and release of inflammatory cytokines, chemokines, cell adhesion molecules, and matrix metalloproteinases that consequently induce tissue remodeling and promote the migration and infiltration of inflammatory cells. This creates a local inflammatory microenvironment, which finally leads to the initiation and progression of neurovascular and cardiovascular diseases.

Contributions to this Special Issue will provide insight into the mechanisms through which endothelial cell activation contributes to the pathogenesis of vascular complications and diseases. A better understanding of these mechanisms would provide an opportunity to prevent and treat vascular disorders triggered and advanced by endothelial dysfunction.

Topics of interest to this Special Issue include but are not limited to:

  • Mechanism of endothelial cell dysfunction;
  • Mediators of endothelial dysfunction;
  • Endothelial cells as a target for drug therapy;
  • Senescence of endothelial cells/senolysis of endothelial cells;
  • The senescence-associated secretory phenotype of endothelial cells;
  • Endothelial inflammaging;
  • Structural remodeling of the artery wall;
  • Activation of Nf-κB, MAPKs, and mTOR pathways in endothelial cells;
  • The effect of acquired risk factors (smoking, alcohol abuse, obesity, etc.) on endothelial cells;
  • The effect of oxidative stress on endothelial cells;
  • Crosstalk between activated/dysfunctional endothelial cells and other cell types, e.g., smooth muscle cells and inflammatory cells.

Dr. Sajjad Muhammad
Guest Editor

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Keywords

  • endothelial dysfunction
  • endothelial cell senescence
  • endothelial cell senolysis
  • senescence-associated secretory phenotype
  • matrix metalloproteinases
  • inflammation
  • inflammaging
  • Nf-κB
  • MAPKs
  • mTOR pathway
  • vascular disorders
  • alcohol abuse
  • smoking
  • hypertension
  • shear stress
  • oxidative stress
  • cardiovascular diseases
  • neurovascular diseases
  • cardiovascular pathophysiology
  • neurovascular pathophysiology

Published Papers (4 papers)

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Research

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15 pages, 1898 KiB  
Article
Sex Influence on Autophagy Markers and miRNAs in Basal and Angiotensin II-Treated Human Umbilical Vein Endothelial Cells
by Flavia Franconi, Giampiero Capobianco, Giuseppe Diana, Valeria Lodde, Alberto De Donno, Maria Laura Idda, Andrea Montella and Ilaria Campesi
Int. J. Mol. Sci. 2023, 24(19), 14929; https://doi.org/10.3390/ijms241914929 - 05 Oct 2023
Cited by 1 | Viewed by 1331
Abstract
Cardiovascular diseases (CVD) display many sex and gender differences, and endothelial dysfunction, angiotensin II (Ang II), and autophagy represent key factors in the autophagic process Therefore, we studied whether Ang II modulates the mentioned processes in a sex-specific way in HUVECs obtained from [...] Read more.
Cardiovascular diseases (CVD) display many sex and gender differences, and endothelial dysfunction, angiotensin II (Ang II), and autophagy represent key factors in the autophagic process Therefore, we studied whether Ang II modulates the mentioned processes in a sex-specific way in HUVECs obtained from healthy male and female newborns. In basal HUVECs, the Parkin gene and protein were higher in FHUVECs than in MHUVECs, while the Beclin-1 protein was more expressed in MHUVECs, and no other significant differences were detected. Ang II significantly increases LAMP-1 and p62 protein expression and decreases the expression of Parkin protein in comparison to basal in MHUVECs. In FHUVECs, Ang II significantly increases the expression of Beclin-1 gene and protein, and Parkin gene. The LC3 II/I ratio and LAMP-1 protein were significantly higher in MHUVECs than in FHUVECs, while Parkin protein was significantly more expressed in Ang II-treated FHUVECs than in male cells. Ang II affects the single miRNA levels: miR-126-3p and miR-133a-3p are downregulated and upregulated in MHUVECs and FHUVECs, respectively. MiR-223 is downregulated in MHUVEC and FHUVECs. Finally, miR-29b-3p and miR-133b are not affected by Ang II. Ang II effects and the relationship between miRNAs and organelles-specific autophagy is sex-dependent in HUVECs. This could lead to a better understanding of the mechanisms underlying sex differences in endothelial dysfunction, providing useful indications for innovative biomarkers and personalized therapeutic approaches. Full article
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16 pages, 2612 KiB  
Article
Elevated Blood Pressure Occurs without Endothelial Dysfunction in a Rat Model of Pulmonary Emphysema
by Elodie Desplanche, Pierre-Edouard Grillet, Quentin Wynands, Patrice Bideaux, Laurie Alburquerque, Azzouz Charrabi, Arnaud Bourdin, Olivier Cazorla, Fares Gouzi and Anne Virsolvy
Int. J. Mol. Sci. 2023, 24(16), 12609; https://doi.org/10.3390/ijms241612609 - 09 Aug 2023
Cited by 1 | Viewed by 974
Abstract
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease involving airway closure and parenchyma destruction (emphysema). Cardiovascular diseases are the main causes of morbi-mortality in COPD and, in particular, hypertension and heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link [...] Read more.
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease involving airway closure and parenchyma destruction (emphysema). Cardiovascular diseases are the main causes of morbi-mortality in COPD and, in particular, hypertension and heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link has currently been established between the onset of COPD, elevated blood pressure (BP) and systemic vascular impairment (endothelial dysfunction). Thus, we aimed to characterize BP and vascular function and remodeling in a rat model of exacerbated emphysema focusing on the role of sympathetic hyperactivity. Emphysema was induced in male Wistar rats by four weekly pulmonary instillations of elastase (4UI) and exacerbation by a single dose of lipopolysaccharides (LPS). Five weeks following the last instillation, in vivo and ex vivo cardiac and vascular functions were investigated. Exacerbated emphysema induced cardiac dysfunction (HFpEF) and a BP increase in this COPD model. We observed vasomotor changes and hypotrophic remodeling of the aorta without endothelial dysfunction. Indeed, changes in contractile and vasorelaxant properties, though endothelium-dependent, were pro-relaxant and NO-independent. A β1-receptor antagonist (bisoprolol) prevented HFpEF and vascular adaptations, while the effect on BP increase was partial. Endothelial dysfunction would not trigger hypertension and HFpEF in COPD. Vascular changes appeared as an adaptation to the increased BP. The preventing effect of bisoprolol revealed a pivotal role of sympathetic hyperactivation in BP elevation. The mechanistic link between HFpEF, cardiac sympathetic activation and BP deserves further studies in this exacerbated-emphysema model, as well as in COPD patients. Full article
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17 pages, 33422 KiB  
Article
Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children
by Jihoon Kim, Chisato Shimizu, Ming He, Hao Wang, Hal M. Hoffman, Adriana H. Tremoulet, John Y.-J. Shyy and Jane C. Burns
Int. J. Mol. Sci. 2023, 24(15), 12318; https://doi.org/10.3390/ijms241512318 - 01 Aug 2023
Cited by 2 | Viewed by 1380
Abstract
Although Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share some clinical manifestations, their cardiovascular outcomes are different, and this may be reflected at the level of the endothelial cell (EC). We performed RNA-seq on cultured ECs incubated with pre-treatment sera [...] Read more.
Although Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share some clinical manifestations, their cardiovascular outcomes are different, and this may be reflected at the level of the endothelial cell (EC). We performed RNA-seq on cultured ECs incubated with pre-treatment sera from KD (n = 5), MIS-C (n = 7), and healthy controls (n = 3). We conducted a weighted gene co-expression network analysis (WGCNA) using 935 transcripts differentially expressed between MIS-C and KD using relaxed filtering (unadjusted p < 0.05, >1.1-fold difference). We found seven gene modules in MIS-C, annotated as an increased TNFα/NFκB pathway, decreased EC homeostasis, anti-inflammation and immune response, translation, and glucocorticoid responsive genes and endothelial–mesenchymal transition (EndoMT). To further understand the difference in the EC response between MIS-C and KD, stringent filtering was applied to identify 41 differentially expressed genes (DEGs) between MIS-C and KD (adjusted p < 0.05, >2-fold-difference). Again, in MIS-C, NFκB pathway genes, including nine pro-survival genes, were upregulated. The expression levels were higher in the genes influencing autophagy (UBD, EBI3, and SQSTM1). Other DEGs also supported the finding by WGCNA. Compared to KD, ECs in MIS-C had increased pro-survival transcripts but reduced transcripts related to EndoMT and EC homeostasis. These differences in the EC response may influence the different cardiovascular outcomes in these two diseases. Full article
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Review

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14 pages, 768 KiB  
Review
The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review
by Dilaware Khan, Jan Frederick Cornelius and Sajjad Muhammad
Int. J. Mol. Sci. 2023, 24(18), 14218; https://doi.org/10.3390/ijms241814218 - 18 Sep 2023
Cited by 5 | Viewed by 1392
Abstract
Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB) is the major driver of inflammation. It increases the [...] Read more.
Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture. After a systematic search, abstract screening, and full-text screening, 30 research articles were included in the review. In this systematic review, we summarized the scientific literature reporting findings on NF-κB’s role in the pathogenesis of IAs. In conclusion, the activation of the NF-κB pathway was associated with IA formation, progression, and rupture. Full article
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