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Life
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New Insights into the Endothelial Dysfunction
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New Insights into the Endothelial Dysfunction

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 11251

Special Issue Editors

Dr. Raffaele Maio

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Guest Editor
Geriatrics Unit, Azienda Ospedaliero Universitaria “Mater Domini”, 88100 Catanzaro, Italy
Interests: hypertension; endothelial dysfunction; ischemic heart disease; arrhythmia; target organ damage; cardiovascular risk factors
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Maria Perticone

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences, University Magna Græcia, 88100 Catanzaro, Italy
Interests: obesity; type-2 diabetes; metabolic syndrome; endothelial dysfunction; hypertension; target organ damage
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Francesco Perticone

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences, University Magna Græcia, 88100 Catanzaro, Italy
Interests: endothelial dysfunction; arterial stiffness; hypertension; atherosclerosis; metabolic syndrome; diabetes mellitus; cardiovascular risk; insulin resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular and metabolic diseases still represent the leading cause of morbidity and mortality worldwide. Cardiovascular and metabolic risk factors, due to the interaction between environment and genetic background, represent the main pathogenetic mechanisms underlying atherosclerotic vascular disease. For these reasons, endothelial alterations, first functional and then morphological, represent the primum movens of the appearance and progression of atherosclerotic vascular damage. In this context, it is well established that endothelial activation/dysfunction, characterized by a reduced nitric oxide bioavailability as a consequence of increased oxidative stress, represents the common factor of vascular damage observed in several haemodynamic, metabolic and inflammatory conditions. It is of interest to consider the emerging role that immune-mediated inflammation plays in the development of vascular damage, representing a new pathogenetic and therapeutic scenario.

Another relevant aspect of the research in this field is the role that inflammation plays in the development of the atherosclerotic lesion. In this context, an important role is played by the inflammatory response and the immune system and their interaction with lipoprotein and endothelium.

Therefore, the understanding of the different mechanisms underlying endothelial activation/dysfunction could be an interesting research field for the development of strategies that can reduce the burden of cardiovascular diseases and their outcomes.

Dr. Raffaele Maio
Prof. Dr. Maria Perticone
Prof. Dr. Francesco Perticone
Guest Editors

Manuscript Submission Information

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Keywords

  • endothelium
  • Cardiovascular disease
  • inflammation
  • risk factors

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Published Papers (5 papers)

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Research

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11 pages, 619 KiB  
Article
Serum Angiopoietin-like Protein 3 Levels Are Associated with Endothelial Function in Patients with Maintenance Hemodialysis
by Tzu-Chiang Wu, Bang-Gee Hsu, Chiu-Huang Kuo, Chih-Hsien Wang and Jen-Pi Tsai
Life 2024, 14(1), 18; https://doi.org/10.3390/life14010018 - 21 Dec 2023
Cited by 1 | Viewed by 962
Abstract
Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We [...] Read more.
Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We enrolled 116 patients on MHD and obtained their blood test results from their medical records. Using a noninvasive digital thermal monitor, we determined the vascular reactivity index (VRI) as a measure of endothelial function. Serum ANGPTL3 concentration was measured by a commercial-enzyme-linked immunosorbent assay. Vascular reactivity was classified as poor in 17 (14.7%) patients, intermediate (1.0 ≤ VRI < 2.0) in 50 (43.1%) patients, and high (VRI ≥ 2.0) in 49 (42.2%) patients. Serum levels of ANGPTL3 (p < 0.001) and alkaline phosphatase (ALP, p = 0.025) increased significantly as the VRI decreased. The log-transformed serum ALP (log-ALP, r = −0.187, p = 0.045) and log-ANGPTL3 (r = −0.319, p < 0.001) showed a negative correlation with the VRI on univariate linear regression analysis. A significant negative correlation was found between log-ANGPTL3 and VRI (p < 0.001) on multivariate stepwise linear regression analysis. The findings of our investigation showed that, in patients with MHD, the ANGPTL3 concentration had a negative correlation with the VRI. Full article
(This article belongs to the Special Issue New Insights into the Endothelial Dysfunction)
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12 pages, 1467 KiB  
Article
Early Signs of Microvascular Endothelial Dysfunction in Adolescents with Newly Diagnosed Essential Hypertension
by Tomas Jurko, Michal Mestanik, Andrea Mestanikova, Kamil Zeleňák and Alexander Jurko
Life 2022, 12(7), 1048; https://doi.org/10.3390/life12071048 - 13 Jul 2022
Cited by 3 | Viewed by 1605
Abstract
Endothelial dysfunction represents one of the key pathomechanisms in many diseases, including hypertension. Peripheral arterial tonometry (PAT) evaluates the functional status of microvascular endothelium and offers a biomarker of early, potentially reversible, vascular damage. This study aimed to assess endothelial function using conventional [...] Read more.
Endothelial dysfunction represents one of the key pathomechanisms in many diseases, including hypertension. Peripheral arterial tonometry (PAT) evaluates the functional status of microvascular endothelium and offers a biomarker of early, potentially reversible, vascular damage. This study aimed to assess endothelial function using conventional and novel indices of PAT in pediatric hypertensives. As such, 100 adolescents with normal blood pressure, and essential and white-coat hypertension were examined using EndoPAT 2000. Conventional reactive hyperemia index (RHI) and novel indices of hyperemic response, including the area under the curve of hyperemic response (AUC), were evaluated. AUC was the only parameter sensitive to the effect of hypertension, with significantly lower values in essential hypertensives compared to normotensives and white-coat hypertensives (p = 0.024, p = 0.032, respectively). AUC was the only parameter significantly correlating with mean ambulatory monitored blood pressure (r = −0.231, p = 0.021). AUC showed a significant negative association with age (p = 0.039), but a significant positive association with pubertal status indexed by plasma levels of dehydroepiandrosterone (p = 0.027). This is the first study reporting early signs of microvascular endothelial dysfunction evaluated using PAT in adolescents with newly diagnosed essential hypertension. Detailed analysis of hyperemic response using overall magnitude indexed by AUC provided a more robust method compared to the conventional evaluation of RHI. Full article
(This article belongs to the Special Issue New Insights into the Endothelial Dysfunction)
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Review

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17 pages, 1186 KiB  
Review
Endothelial Dysfunction and Heart Failure with Preserved Ejection Fraction—An Updated Review of the Literature
by Mariarosaria De Luca, Giulia Crisci, Giuseppe Armentaro, Sebastiano Cicco, Giovanni Talerico, Emanuele Bobbio, Lorena Lanzafame, Christopher G. Green, Abbie G. McLellan, Radek Debiec, Paolo Caferra, Roberto Scicali, Antonio Cannatà, Muhammad Zubair Israr, Liam M. Heaney and Andrea Salzano
Life 2024, 14(1), 30; https://doi.org/10.3390/life14010030 - 24 Dec 2023
Cited by 2 | Viewed by 2126
Abstract
Heart failure (HF) is a clinical syndrome consisting of typical symptoms and signs due to structural and/or functional abnormalities of the heart, resulting in elevated intracardiac pressures and/or inadequate cardiac output. The vascular system plays a crucial role in the development and progression [...] Read more.
Heart failure (HF) is a clinical syndrome consisting of typical symptoms and signs due to structural and/or functional abnormalities of the heart, resulting in elevated intracardiac pressures and/or inadequate cardiac output. The vascular system plays a crucial role in the development and progression of HF regardless of ejection fraction, with endothelial dysfunction (ED) as one of the principal features of HF. The main ED manifestations (i.e., impaired endothelium-dependent vasodilation, increased oxidative stress, chronic inflammation, leukocyte adhesion, and endothelial cell senescence) affect the systemic and pulmonary haemodynamic and the renal and coronary circulation. The present review is aimed to discuss the contribution of ED to HF pathophysiology—in particular, HF with preserved ejection fraction—ED role in HF patients, and the possible effects of pharmacological and non-pharmacological approaches. For this purpose, relevant data from a literature search (PubMed, Scopus, EMBASE, and Medline) were reviewed. As a result, ED, assessed via venous occlusion plethysmography or flow-mediated dilation, was shown to be independently associated with poor outcomes in HF patients (e.g., mortality, cardiovascular events, and hospitalization due to worsening HF). In addition, SGLT2 inhibitors, endothelin antagonists, endothelial nitric oxide synthase cofactors, antioxidants, and exercise training were shown to positively modulate ED in HF. Despite the need for future research to better clarify the role of the vascular endothelium in HF, ED represents an interesting and promising potential therapeutic target. Full article
(This article belongs to the Special Issue New Insights into the Endothelial Dysfunction)
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19 pages, 1548 KiB  
Review
Inflammatory Mediators of Endothelial Dysfunction
by Eirini Dri, Evangelos Lampas, George Lazaros, Emilia Lazarou, Panagiotis Theofilis, Costas Tsioufis and Dimitris Tousoulis
Life 2023, 13(6), 1420; https://doi.org/10.3390/life13061420 - 20 Jun 2023
Cited by 18 | Viewed by 3294
Abstract
Endothelial dysfunction (ED) is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), and inflammatory factors, as well as deficiency of nitric oxide (NO) bioavailability. It has been reported that the maintenance of endothelial cell integrity serves a significant role in [...] Read more.
Endothelial dysfunction (ED) is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), and inflammatory factors, as well as deficiency of nitric oxide (NO) bioavailability. It has been reported that the maintenance of endothelial cell integrity serves a significant role in human health and disease due to the involvement of the endothelium in several processes, such as regulation of vascular tone, regulation of hemostasis and thrombosis, cell adhesion, smooth muscle cell proliferation, and vascular inflammation. Inflammatory modulators/biomarkers, such as IL-1α, IL-1β, IL-6, IL-12, IL-15, IL-18, and tumor necrosis factor α, or alternative anti-inflammatory cytokine IL-10, and adhesion molecules (ICAM-1, VCAM-1), involved in atherosclerosis progression have been shown to predict cardiovascular diseases. Furthermore, several signaling pathways, such as NLRP3 inflammasome, that are associated with the inflammatory response and the disrupted H2S bioavailability are postulated to be new indicators for endothelial cell inflammation and its associated endothelial dysfunction. In this review, we summarize the knowledge of a plethora of reviews, research articles, and clinical trials concerning the key inflammatory modulators and signaling pathways in atherosclerosis due to endothelial dysfunction. Full article
(This article belongs to the Special Issue New Insights into the Endothelial Dysfunction)
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Other

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14 pages, 1436 KiB  
Systematic Review
Endothelial Dysfunction in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
by Panagiotis Theofilis, Aikaterini Vordoni, Nikolaos Nakas and Rigas G. Kalaitzidis
Life 2022, 12(5), 718; https://doi.org/10.3390/life12050718 - 11 May 2022
Cited by 14 | Viewed by 2421
Abstract
Individuals with nonalcoholic fatty liver disease (NAFLD) are characterized by increased cardiovascular risk. Endothelial dysfunction, a mechanism implicated in those processes, may constitute the missing link in this interaction. Therefore, this systematic review and meta-analysis aims to evaluate the association of endothelial dysfunction, [...] Read more.
Individuals with nonalcoholic fatty liver disease (NAFLD) are characterized by increased cardiovascular risk. Endothelial dysfunction, a mechanism implicated in those processes, may constitute the missing link in this interaction. Therefore, this systematic review and meta-analysis aims to evaluate the association of endothelial dysfunction, assessed by flow-mediated dilation (FMD) of the brachial artery, with NAFLD. We conducted a systematic literature search for studies assessing the difference in FMD between patients with NAFLD and controls. Exclusion criteria consisted of preclinical studies, studies in children/adolescents, no FMD assessment, and the absence of an NAFLD/control group. The database search identified 96 studies. Following the application of the exclusion criteria, 22 studies were included in the meta-analysis (NAFLD: 2164 subjects; control: 3322 subjects). Compared with controls, patients with NAFLD had significantly lower FMD% values (SMD: −1.37, 95% CI −1.91 to −0.83, p < 0.001, I2: 98%). Results remained unaffected after exclusion of any single study. Subgroup analysis revealed significantly decreased FMD in NAFLD subjects diagnosed with liver ultrasound or liver biopsy compared with method combination or other methods, while no differences were observed according to the chosen cuff inflation threshold, the presence of a significant difference in obesity measures between the groups, or the type of the control group (age- and sex-matched vs. other). Funnel plot asymmetry was not observed. Finally, compared with patients with pure steatosis, individuals with nonalcoholic steatohepatitis had significantly lower FMD (SMD: −0.81, 95% CI −1.51 to −0.31, p = 0.003, I2: 81%). In conclusion, FMD of the brachial artery, indicative of endothelial dysfunction, was significantly reduced in subjects with nonalcoholic fatty liver disease. Patients with nonalcoholic steatohepatitis might be facing a more pronounced endothelial impairment. Full article
(This article belongs to the Special Issue New Insights into the Endothelial Dysfunction)
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