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Endothelial Function and Cardiovascular Disease: Molecular Advances and Challenges

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: 20 August 2025 | Viewed by 891

Special Issue Editor


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Guest Editor
Department of Translational Medicine, University Eastern Piedmont, 28100 Novara, Italy
Interests: oxidative stress; cardiac function; mitochondrial function; aging; nitric oxide; physiology; NAFLD; microvesicles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The keeping endothelial function plays a central role for the regulation of physiologic processes related to the cardiovascular system. In general, endothelial activation, inflammation, and oxidative stress may represent the starting points leading to later events, like endothelial-to-mesenchymal transition and endothelial apoptosis, which result in the loss of endothelial function and the genesis of various cardiovascular diseases. This phenomenon has a multifactorial nature, being influenced by genetics and aging, as well as lifestyle.

Understanding the dynamic interplay between the above causes and traditional risks factors is crucial for the prevention of cardiovascular diseases and to tailor therapeutic interventions focused on the treatment of the different pathologies by targeting the underlying mechanism(s).

Speaking about molecular advances, pathways related to endothelial senescence, such as those involving sirtuins, klotho, and nuclear factor-E2-related factor 2 (NRF2), could represent interesting and innovative therapeutic targets to treat or prevent cardiovascular aging and age-related vascular pathologies. Also, endothelium-derived vesicles could act both as biomarkers and contributors to the onset and progression of cardiovascular diseases and represent challenges.

The aim of this Special Issue is to collect information about innovative aspects related to the regulation of endothelial functions and about their role in the genesis of cardiovascular diseases. Thanks to the knowledge of molecular advances in this field, it could be possible to gain a comprehensive understanding of endothelial dysfunctions and to develop strategies to mitigate their impact on cardiovascular diseases’ onset and progression.

Dr. Elena Grossini
Guest Editor

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Keywords

  • endothelium
  • heart
  • protection
  • therapeutic strategies
  • vascular system
  • vesicles

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Published Papers (2 papers)

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Research

15 pages, 608 KiB  
Article
Assessment of Blood Endothelial Cell Biomarkers in Women and Men with Abnormal Body Mass and Paroxysmal Atrial Fibrillation Based on CHA2DS2-VASC Score: A Retrospective Study
by Wiesław Sikora, Dominika Kanikowska, Jan Budzianowski, Edyta Kawka, Rafał Rutkowski and Katarzyna Korybalska
Int. J. Mol. Sci. 2025, 26(8), 3627; https://doi.org/10.3390/ijms26083627 - 11 Apr 2025
Viewed by 143
Abstract
Endothelial dysfunction (ED) promotes and maintains atrial fibrillation (AF). Using a CHA2DS2-VASc score in women and men with paroxysmal AF, we aimed to determine which patients’ ED would be more pronounced. We recruited 47 females and 48 males (mean BMI 31 kg/m2 [...] Read more.
Endothelial dysfunction (ED) promotes and maintains atrial fibrillation (AF). Using a CHA2DS2-VASc score in women and men with paroxysmal AF, we aimed to determine which patients’ ED would be more pronounced. We recruited 47 females and 48 males (mean BMI 31 kg/m2 and 30 kg/m2, respectively) with paroxysmal AF and abnormal body mass and divided them into those with low (F < 3; M < 2) and high (F ≥ 3; M ≥ 2) CHA2DS2-VASC score. The blood samples were taken before AF ablation. Using Elisa tests, we measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule (sICAM-1), von Willebrand factor (vWF), and thrombomodulin (sTM). ED was more pronounced in females, expressed by higher endothelial cell marker concentrations: sVCAM-1 and sTM in low scores and sICAM-1 in high scores, CHA2DS2-VASc. Females were characterized by postmenopausal status, higher risk of thrombosis, lower GFR, and more frequent treatment with antiarrhythmic drugs. In contrast, males have only higher suppression of tumorigenicity 2 (ST2). In conclusion, women with paroxysmal AF exhibited more pronounced ED compared to men, regardless of their CHA2DS2-VASc scores. The soluble pro-inflammatory adhesion molecules and thrombomodulin emerge as the most sensitive biomarkers of ED elevated in females. Full article
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25 pages, 5834 KiB  
Article
Characterization of Circulating Vesicles of Complicated and Uncomplicated Systemic Sclerosis Patients and Their Role in Vascular Dysfunction
by Elena Grossini, Mattia Bellan, Sakthipriyan Venkatesan, Mohammad Mostafa Ola Pour, Marco Mennuni, Domenico D’Amario, Stefania Bruno, Daniela Ferrante, Daniela Capello, Pier Paolo Sainaghi, Mario Pirisi and Giuseppe Patti
Int. J. Mol. Sci. 2025, 26(6), 2380; https://doi.org/10.3390/ijms26062380 - 7 Mar 2025
Viewed by 488
Abstract
Extracellular vesicles (EVs) could be involved in the onset of systemic sclerosis (SSc) through the modulation of vascular function. Anyway, available data are contradictory, and further investigation would be necessary to clarify this aspect. Here, we characterized circulating EVs isolated from SSc patients [...] Read more.
Extracellular vesicles (EVs) could be involved in the onset of systemic sclerosis (SSc) through the modulation of vascular function. Anyway, available data are contradictory, and further investigation would be necessary to clarify this aspect. Here, we characterized circulating EVs isolated from SSc patients and evaluated their effects on human vascular endothelial cells (HUVECs) and smooth muscle cells. In EVs from 13 complicated and 27 uncomplicated SSc patients and five healthy controls (HCs), we analyzed the size, concentration, and surface marker expression. In addition, EVs were used to stimulate HUVECs, and we evaluated cell viability, mitochondrial membrane potential, and nitric oxide (NO) and mitochondrial reactive oxygen species (MitoROS) release. In smooth muscle cells, the effects of EVs on calcium movement were examined. The results showed that the EVs of SSc patients expressed markers of T-lymphocyte/platelet/endothelial cell origin and were larger and more concentrated than those from HCs. In addition, the EVs of SSc patients reduced cell viability and mitochondrial membrane potential and increased NO and MitoROS release in HUVECs and intracellular calcium in smooth muscle cells. In conclusion, we found a specific pattern for EVs isolated from SSc patients, which could have a pathogenic role through direct actions on endothelial and smooth muscle cells. Full article
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