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Endothelial Dysfunction and Its Related Cardiometabolic Disorders: From Mechanisms to Targeted Therapies

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 March 2025 | Viewed by 933

Special Issue Editor


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Guest Editor
Department of Precision and Regenerative Medicine and Ionian Area, School of Medicine, University of Bari «Aldo Moro», Bari, Italy
Interests: endothelial dysfunction; nitric oxide; endothelial mediators; biomarkers; adiponectin; diabetes; cardiovascular disease; inflammation; perivascular adipose tissue

Special Issue Information

Dear Colleagues,

Endothelial dysfunction represents the earliest sign of both cardiovascular and metabolic disorders, as well as a common underlying mechanism in the pathogenesis of such ailments. The renowned impact that metabolic abnormalities such as hyperglycemia, insulin resistance, hyperinsulinemia, and hyperlipidemia exert on endothelial dysfunction has been linked to pro-oxidative and pro-inflammatory mechanisms that impair endothelial cell functionality, leading to the dysregulation of the endothelial NO-synthase (eNOS) pathway. Several mechanisms may participate in eNOS dysfunctions, such as eNOS dimerization and uncoupling, modified eNOS expression/activity, the genetic polymorphism of eNOS gene, altered eNOS signaling regulation, and the epigenetic regulation of eNOS expression.

The search for specific and sensitive biomarkers of endothelial dysfunction is an ongoing actively pursued field, in which the clinical theragnostic potential extends from the validation of novel criteria for identifying at-risk subjects and monitoring the effectiveness of current treatments, to the recognition and discovery of additional therapeutic targets.

Endothelial adhesion molecules, cytokines, oxidized low density lipoproteins (Ox-LDL), circulating endothelial microparticles, and asymmetric dimethylarginine (ADMA) levels are among the putative biomarkers of endothelial activation and dysfunction that have been identified thus far. Recent evidence suggests that endothelial progenitor cell (EPC) dysfunction, alterations in the gut microbiota, and microRNA released by extracellular vesicles may also play a role in the development of cardiovascular impairment under dysmetabolic disturbances.

The goal of this Special Issue is to help to bridge the gap between molecular mechanisms involved in the onset of endothelial dysfunction and the potential therapeutic strategies targeting the pathophysiological pathways behind endothelial dysfunction and its related cardiometabolic disorders.

For this purpose, original research articles and novel review articles focusing on molecular and clinical approaches to identify predictive biomarkers are welcome.

Dr. Nacci Carmela
Guest Editor

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Keywords

  • endothelial dysfunction
  • endothelial activation
  • endothelial nitric oxide synthase
  • cardiometabolic disease
  • vascular inflammation
  • chemokines
  • adipocytokines
  • atherosclerosis
  • diabetes
  • biomarkers

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Published Papers (1 paper)

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Research

16 pages, 1042 KiB  
Article
Endothelial Dysfunction with Aging: Does Sex Matter?
by Jakub Jozue Wojtacha, Barbara Morawin, Edyta Wawrzyniak-Gramacka, Anna Tylutka, Ana Karyn Ehrenfried de Freitas and Agnieszka Zembron-Lacny
Int. J. Mol. Sci. 2024, 25(22), 12203; https://doi.org/10.3390/ijms252212203 - 13 Nov 2024
Viewed by 570
Abstract
Oxidative stress and inflammation accompany endothelial dysfunction that results from the excessive or uncontrolled production of reactive oxygen and nitrogen species (RONS) in older adults. This study was designed to assess the usefulness of serum oxi-inflammatory component combinations in vascular disease prediction and [...] Read more.
Oxidative stress and inflammation accompany endothelial dysfunction that results from the excessive or uncontrolled production of reactive oxygen and nitrogen species (RONS) in older adults. This study was designed to assess the usefulness of serum oxi-inflammatory component combinations in vascular disease prediction and prevention with regard to sex. Women (n = 145) and men (n = 50) aged 72.2 ± 7.8 years participated in this project. The females demonstrated the elevated production of hydrogen peroxide (H2O2) and nitric oxide (NO) responsible for intravascular low-density lipoprotein oxidation. NO generation was enhanced in the women, but its bioavailability was reduced, which was expressed by a high 3-nitrotyrosine (3-NitroT) concentration. The relation of NO/3-NitroT (rs = 0.811, p < 0.001) in the women and NO/3-NitroT (rs = −0.611, p < 0.001) in the men showed that sex determines endothelial dysfunction. RONS generation in the women simultaneously promoted endothelial regeneration, as demonstrated by a ~1.5-fold increase in circulating progenitor cells. Inflammation-specific variables, such as the neutrophil-to-lymphocyte ratio, the systemic immune inflammation index, and the neutrophil-to-high-density lipoprotein (HDL) ratio, were reduced in the women and showed their diagnostic utility for clinical prognosis in vascular dysfunction, especially the C-reactive-protein-to-HDL ratio (AUC = 0.980, specificity 94.7%, sensitivity 93.3%, OR = 252, 95% CI 65–967, p < 0.001). This study is the first to have revealed sex-specific changes in the oxi-inflammatory response, which can generate the risk of cardiovascular events at an older age. Full article
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