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Novel Therapeutic Approaches for Endothelial Dysfunction
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Novel Therapeutic Approaches for Endothelial Dysfunction

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 4646

Special Issue Editor

Dr. Alma Martelli

E-Mail Website
Guest Editor
1. Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
2. Interdepartmental Research Centre "Nutraceuticals and Food for Health (NUTRAFOOD)", University of Pisa, 56126 Pisa, Italy
3. Interdepartmental Research Centre of "Ageing Biology and Pathology", University of Pisa, 56126 Pisa, Italy
Interests: cardiovascular pharmacology; gasotransmitters; nutraceuticals; hydrogen sulfide; brassicaceae; isothiocyanates; vascular inflammation; aging; endothelial dysfunction; hypertension; H2S-donors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The preservation of vascular wall integrity and functionality is an unmet medical need. The vascular tree is frequently the first target of slowly progressive degeneration caused by ageing, fat-rich diet, or metabolic diseases. These factors affect the integrity of endothelium and its “barrier” function, supporting the onset of atherosclerotic plaque and spreading inflammation. Consequent endothelial dysfunction leads to decreased nitric oxide (NO) biosynthesis, impaired regulation of vascular tone, and platelet aggregation, which are prodromic of hypertension and coagulopathy. More rarely, a massive endothelial disruption was induced by acute inflammatory events like such as bacterial or viral infections, as observed during the last year with the Coronavirus disease (COVID-19), induced by SARS-CoV-2 infection. Indeed, the vascular endothelium was one of the main tissues under attack during the cytokines storm evoked by COVID-19. This attack led to endothelium disruption and a lack of the endothelial main functions, i.e., NO biosynthesis, anti-platelet activity and vasorelaxation. As a consequence, in COVID-19 patients, the injury of endothelial tissue led to coagulopathy and death for stroke or infarction. In this panorama, the protection of the vascular wall and, in particular, of the endothelial tissue, both from progressive slow degeneration, and from acute massive disruption, became fundamental. This Special Issue aims to evaluate and identify therapeutic and/or nutraceutical approaches that can provide an answer to this compelling unmet medical need. Due to the aim of the journal, pure clinical/investigation studies will not suitable, but clinical submissions with biomolecular experiments are welcomed. Additionally, pure model studies are not suitable for IJMS, but model submissions with at least some validate data (or biological experiments) are welcome.

Dr. Alma Martelli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vascular endothelium
  • endothelial dysfunction
  • vascular inflammation
  • vascular diseases
  • nutraceuticals
  • endothelial protection
  • cardiovascular diseases
  • diabetes
  • hypertension
  • ageing
  • cardiovascular drug
  • metabolic diseases
  • metabolic drugs
  • nitric oxide
  • hydrogen sulfide
  • atherosclerosis
  • TMAO
  • cytokine storm
  • Ox-inflamm-ageing

Published Papers (2 papers)

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Research

19 pages, 4479 KiB  
Article
Anti-Inflammatory Effect of the Natural H2S-Donor Erucin in Vascular Endothelium
by Valerio Ciccone, Eugenia Piragine, Era Gorica, Valentina Citi, Lara Testai, Eleonora Pagnotta, Roberto Matteo, Nicola Pecchioni, Rosangela Montanaro, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Vincenzo Brancaleone, Lucia Morbidelli, Vincenzo Calderone and Alma Martelli
Int. J. Mol. Sci. 2022, 23(24), 15593; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232415593 - 09 Dec 2022
Cited by 11 | Viewed by 1737
Abstract
Vascular inflammation (VI) represents a pathological condition that progressively affects the integrity and functionality of the vascular wall, thus leading to endothelial dysfunction and the onset of several cardiovascular diseases. Therefore, the research of novel compounds able to prevent VI represents a compelling [...] Read more.
Vascular inflammation (VI) represents a pathological condition that progressively affects the integrity and functionality of the vascular wall, thus leading to endothelial dysfunction and the onset of several cardiovascular diseases. Therefore, the research of novel compounds able to prevent VI represents a compelling need. In this study, we tested erucin, the natural isothiocyanate H2S-donor derived from Eruca sativa Mill. (Brassicaceae), in an in vivo mouse model of lipopolysaccharide (LPS)-induced peritonitis, where it significantly reduced the amount of emigrated CD11b positive neutrophils. We then evaluated the anti-inflammatory effects of erucin in LPS-challenged human umbilical vein endothelial cells (HUVECs). The pre-incubation of erucin, before LPS treatment (1, 6, 24 h), significantly preserved cell viability and prevented the increase of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) levels. Moreover, erucin downregulated endothelial hyperpermeability and reduced the loss of vascular endothelial (VE)-Cadherin levels. In addition, erucin decreased vascular cell adhesion molecule 1 (VCAM-1), cyclooxygenase-2 (COX-2) and microsomal prostaglandin E-synthase 1 (mPGES-1) expression. Of note, erucin induced eNOS phosphorylation and counteracted LPS-mediated NF-κB nuclear translocation, an effect that was partially abolished in the presence of the eNOS inhibitor L-NAME. Therefore, erucin can control endothelial function through biochemical and genomic positive effects against VI. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Endothelial Dysfunction)
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15 pages, 1102 KiB  
Article
An Optimized MRM-Based Workflow of the l-Arginine/Nitric Oxide Pathway Metabolites Revealed Disease- and Sex-Related Differences in the Cardiovascular Field
by Benedetta Porro, Sonia Eligini, Edoardo Conte, Nicola Cosentino, Nicolò Capra, Viviana Cavalca and Cristina Banfi
Int. J. Mol. Sci. 2022, 23(3), 1136; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031136 - 20 Jan 2022
Viewed by 2188
Abstract
Clinical data indicate that low circulating l-homoarginine (HArg) concentrations are associated with cardiovascular (CV) disease, CV mortality, and all-cause mortality. A high number of LC-based analytical methods for the quantification of HArg, in combination with the l-arginine (Arg)-related pathway metabolites, have [...] Read more.
Clinical data indicate that low circulating l-homoarginine (HArg) concentrations are associated with cardiovascular (CV) disease, CV mortality, and all-cause mortality. A high number of LC-based analytical methods for the quantification of HArg, in combination with the l-arginine (Arg)-related pathway metabolites, have been reported. However, these methods usually consider a limited panel of analytes. Thus, in order to achieve a comprehensive picture of the Arg metabolism, we described an improved targeted metabolomic approach based on a multiple reaction monitoring (MRM) mass spectrometry method for the simultaneous quantification of the Arg/nitric oxide (NO) pathway metabolites. This methodology was then employed to quantify the plasma concentrations of these analytes in a cohort of individuals with different grades/types of coronary artery disease (CAD) in order to increase knowledge about the role of HArg and its associated metabolites in the CV field. Our results showed that the MRM method here implemented is suitable for the simultaneous assessment of a wide panel of amino acids involved in the Arg/NO metabolic pathway in plasma samples from patients with CV disease. Further, our findings highlighted an impairment of the Arg/NO metabolic pathway, and suggest a sex-dependent regulation of this metabolic route. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Endothelial Dysfunction)
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