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Preventive and Therapeutic Strategies in Vascular Dysfunction

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

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 4743

Special Issue Editor

1. Institute of Physiology, iCBR, Faculty of Medicine, University of Coimbra, 3000-354 Coimbra, Portugal
2. Institute of Physiology, Faculty of Medicine, University of Coimbra, Subunit 1, polo 3, Azinhaga de Santa Comba, Celas, 3000-354 Coimbra, Portugal
Interests: lipid peroxidation; neuroprotective agents; blood glucose; endothelium; vascular

Special Issue Information

Dear Colleagues,

In the last two decades, the vascular endothelium has emerged as a bioactive monolayer of cells essential in the control of vascular homeostasis, regulating various processes including vascular tone, permeability, coagulation, thrombosis, cell growth, inflammation, oxidation and angiogenesis. This inner layer of specialized cells facing the lumen of blood vessels is present in arteries, veins and cardiac chambers and acts as a protective barrier between circulating blood and the adjacent tissues.

Endothelial cells release bioactive substances in response to stimuli. The endothelium is prone to direct or indirect injury due to the presence of cardiovascular risk factors (such as chronic disease states, metabolic conditions (for example, diabetes mellitus, obesity, dyslipidemia), smoking and disturbed blood flow). When damaged endothelial cells are activated and trigger an inflammatory response involving other cell types—monocytes, lymphocytes, platelets and smooth muscle cells—this can lead to endothelial cell dysfunction, stiffness of the vessel wall and atherogenic changes in the vascular wall. Endothelial dysfunction is indeed considered a spectrum of phenotypic states. Nitric oxide (NO)-mediated endothelium-dependent dilation in response to blood flow or pharmacological stimuli is an important physiological indicator of endothelial function.

Cardiovascular (CV) disease prevention strategies in 2021 remain a major healthcare issue. Physical activity, healthy diet and therapeutic approaches aiming at improving endothelial function will contribute to the prevention of CV adverse events. Novel nutraceutical compounds able to decrease inflammation and oxidative stress and enhance NO bioavailability are considered a possible complementary strategy to promote optimal endothelial health. In addition, the inclusion of novel risk biomarkers may improve CV risk prediction in clinical practice. Furthermore, new imaging technologies such as molecular imaging for inflammation and metabolism provide new tools and may play a key role in the future.

This Special Issue on vascular dysfunction aims to present research and review papers that may bring novelty to the field and highlight the importance of preventive medicine in cardiovascular medicine.

Dr. Cristina M. Sena
Guest Editor

Manuscript Submission Information

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Keywords

  • Vascular dysfunction
  • oxidative stress
  • inflammation
  • aging
  • non-communicable diseases
  • novel therapeutic approaches

Published Papers (2 papers)

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Research

12 pages, 1601 KiB  
Article
High VEGFR3 Expression Reduces Doxorubicin Efficacy in Triple-Negative Breast Cancer
by Sandra Torres-Ruiz, Eduardo Tormo, Iris Garrido-Cano, Ana Lameirinhas, Federico Rojo, Juan Madoz-Gúrpide, Octavio Burgués, Cristina Hernando, Begoña Bermejo, María Teresa Martínez, Ana Lluch, Juan Miguel Cejalvo and Pilar Eroles
Int. J. Mol. Sci. 2023, 24(4), 3601; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043601 - 10 Feb 2023
Cited by 2 | Viewed by 1467
Abstract
Due to the lack of specific targets, cytotoxic chemotherapy still represents the common standard treatment for triple-negative breast patients. Despite the harmful effect of chemotherapy on tumor cells, there is evidence that treatment could modulate the tumor microenvironment in a way favoring the [...] Read more.
Due to the lack of specific targets, cytotoxic chemotherapy still represents the common standard treatment for triple-negative breast patients. Despite the harmful effect of chemotherapy on tumor cells, there is evidence that treatment could modulate the tumor microenvironment in a way favoring the propagation of the tumor. In addition, the lymphangiogenesis process and its factors could be involved in this counter-therapeutic event. In our study, we have evaluated the expression of the main lymphangiogenic receptor VEGFR3 in two triple-negative breast cancer in vitro models, resistant or not to doxorubicin treatment. The expression of the receptor, at mRNA and protein levels, was higher in doxorubicin-resistant cells than in parental cells. In addition, we confirmed the upregulation of VEGFR3 levels after a short treatment with doxorubicin. Furthermore, VEGFR3 silencing reduced cell proliferation and migration capacities in both cell lines. Interestingly, high VEGFR3 expression was significantly positively correlated with worse survival in patients treated with chemotherapy. Furthermore, we have found that patients with high expression of VEGFR3 present shorter relapse-free survival than patients with low levels of the receptor. In conclusion, elevated VEGFR3 levels correlate with poor survival in patients and with reduced doxorubicin treatment efficacy in vitro. Our results suggest that the levels of this receptor could be a potential marker of meager doxorubicin response. Consequently, our results suggest that the combination of chemotherapy and VEGFR3 blockage could be a potentially useful therapeutic strategy for the treatment of triple-negative breast cancer. Full article
(This article belongs to the Special Issue Preventive and Therapeutic Strategies in Vascular Dysfunction)
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16 pages, 2740 KiB  
Article
Luteolin Improves Perivascular Adipose Tissue Profile and Vascular Dysfunction in Goto-Kakizaki Rats
by Marcelo Queiroz, Adriana Leandro, Lara Azul, Artur Figueirinha, Raquel Seiça and Cristina M. Sena
Int. J. Mol. Sci. 2021, 22(24), 13671; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413671 - 20 Dec 2021
Cited by 3 | Viewed by 2649
Abstract
We investigated the effects of luteolin on metabolism, vascular reactivity, and perivascular adipose tissue (PVAT) in nonobese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats. Methods: Wistar and GK rats were divided in two groups: (1) control groups treated with vehicle; (2) [...] Read more.
We investigated the effects of luteolin on metabolism, vascular reactivity, and perivascular adipose tissue (PVAT) in nonobese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats. Methods: Wistar and GK rats were divided in two groups: (1) control groups treated with vehicle; (2) groups treated with luteolin (10 mg/kg/day, for 2 months). Several metabolic parameters such as adiposity index, lipid profile, fasting glucose levels, glucose and insulin tolerance tests were determined. Endothelial function and contraction studies were performed in aortas with (PVAT+) or without (PVAT−) periaortic adipose tissue. We also studied vascular oxidative stress, glycation and assessed CRP, CCL2, and nitrotyrosine levels in PVAT. Results: Endothelial function was impaired in diabetic GK rats (47% (GK − PVAT) and 65% (GK + PVAT) inhibition of maximal endothelial dependent relaxation) and significantly improved by luteolin treatment (29% (GK − PVAT) and 22% (GK + PVAT) inhibition of maximal endothelial dependent relaxation, p < 0.01). Vascular oxidative stress and advanced glycation end-products’ levels were increased in aortic rings (~2-fold, p < 0.05) of diabetic rats and significantly improved by luteolin treatment (to levels not significantly different from controls). Periaortic adipose tissue anti-contractile action was significantly rescued with luteolin administration (p < 0.001). In addition, luteolin treatment significantly recovered proinflammatory and pro-oxidant PVAT phenotype, and improved systemic and metabolic parameters in GK rats. Conclusions: Luteolin ameliorates endothelial dysfunction in type 2 diabetes and exhibits therapeutic potential for the treatment of vascular complications associated with type 2 diabetes. Full article
(This article belongs to the Special Issue Preventive and Therapeutic Strategies in Vascular Dysfunction)
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