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Vascular Function in Chronic Non-communicable Diseases

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 45980

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Prof. Dr. Manfredi Tesauro

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U.O.C. of Internal Medicine—Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Interests: endothelial dysfunction; obesity; insulin resistance; diabetic nephropathy; metabolic syndrome; adipokines
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Annalisa Noce

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1. UOSD Nephrology and Dialysis, University Hospital Tor Vergata, Rome, Italy
2. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Interests: nutrition in chronic kidney disease; hemodialysis; natural active compounds for prevention of chronic non-communicable diseases; body composition assessment; uremic sarcopenia; oxidative stress; microbiome in CKD; endothelial dysfunction in CKD
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic diseases, in particular non-communicable diseases (NCDs) (like diabetes mellitus, cardiovascular diseases, obesity, cancer, and chronic kidney disease) are one of the major causes of mortality and morbidity worldwide. Currently, the number of people affected by chronic NCDs is much higher than in the past. This data is related to the increase in life expectancy and it is especially valid for countries with a high rate of elderly people. Chronic NCDs, in developed countries, weigh heavily on health expenditure. Dysfunction of endothelium and in the vascular system play a pivotal role in the chronic NCDs pathophysiology. This vascular impairment is, in turn, worsened by an increased production of ROS and in an enhanced release of pro-inflammatory cytokines. Oxidative stress and low-grade chronic inflammatory status are peculiar features of chronic NCDs. Therapeutic strategies useful for counteract vascular involvement and the progression of chronic NCDs include moderate exercise, healthy eating habits and the use of drugs exerting an endothelium-protective action. We welcome the submission of original research articles and review articles on signaling mechanisms, novel therapeutic approaches and clinical observations.

Prof. Manfredi Tesauro
Prof. Annalisa Noce
Guest Editors

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Keywords

chronic non-communicable diseases (NCDs)
vascular function
inflammation
atherosclerosis
diabetes
obesity
metabolic syndrome
kidney disease
cancer
reactive oxygen species
novel therapeutic approach

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

3 pages, 194 KiB

Open AccessEditorial

Vascular Function in Chronic Non-Communicable Diseases

by Manfredi Tesauro and Annalisa Noce

Biomedicines 2022, 10(10), 2520; https://doi.org/10.3390/biomedicines10102520 - 9 Oct 2022

Viewed by 1192

Abstract

Chronic non-communicable diseases (CNCDs) are one of the major causes of mortality and morbidity worldwide [...] Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

Research

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19 pages, 2807 KiB

Open AccessArticle

Alpha-Lipoic Acid Supplementation Restores Early Age-Related Sensory and Endothelial Dysfunction in the Skin

by Anne-France de Bengy, Johanna Decorps, Lisa S. Martin, Aurélie Pagnon, Fabien P. Chevalier, Dominique Sigaudo-Roussel and Bérengère Fromy

Biomedicines 2022, 10(11), 2887; https://doi.org/10.3390/biomedicines10112887 - 10 Nov 2022

Cited by 3 | Viewed by 2757

Abstract

Many changes characterize skin aging, and the resulting dysfunctions still constitute a real challenge for our society. The aim of this study was to compare the skin aging of two rat strains, Wistar and Brown Norway (BN), considered as “poorly aging” and “healthy aging” models, respectively, and to assess the effect of alpha-lipoic acid (LPA), especially on skin microcirculation. To this purpose, various skin characteristics were studied at 6, 12, and 24 months and compared to the results of LPA treatment performed at 12 or 24 months. Skin aging occurred in both strains, but we showed an early occurrence of different age-related disorders in the Wistar strain compared to BN strain, especially regarding weight gain, glycemia dysregulation, basal skin perfusion, endothelial function, and skin resistance to low pressure. LPA treatment tended to improve skin resistance to low pressure in BN but not in Wistar despite the improvement of basal skin perfusion, endothelial function, and skin sensory sensitivity. Overall, this study confirmed the healthier aging of BN compared to Wistar strain and the positive effect of LPA on both general state and skin microcirculation. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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17 pages, 2272 KiB

Open AccessArticle

Identification of Potential Targets Linked to the Cardiovascular/Alzheimer’s Axis through Bioinformatics Approaches

by Francisco Andújar-Vera, Cristina García-Fontana, Raquel Sanabria-de la Torre, Sheila González-Salvatierra, Luis Martínez-Heredia, Iván Iglesias-Baena, Manuel Muñoz-Torres and Beatriz García-Fontana

Biomedicines 2022, 10(2), 389; https://doi.org/10.3390/biomedicines10020389 - 6 Feb 2022

Cited by 2 | Viewed by 3478

Abstract

The identification of common targets in Alzheimer’s disease (AD) and cardiovascular disease (CVD) in recent years makes the study of the CVD/AD axis a research topic of great interest. Besides aging, other links between CVD and AD have been described, suggesting the existence of common molecular mechanisms. Our study aimed to identify common targets in the CVD/AD axis. For this purpose, genomic data from calcified and healthy femoral artery samples were used to identify differentially expressed genes (DEGs), which were used to generate a protein–protein interaction network, where a module related to AD was identified. This module was enriched with the functionally closest proteins and analyzed using different centrality algorithms to determine the main targets in the CVD/AD axis. Validation was performed by proteomic and data mining analyses. The proteins identified with an important role in both pathologies were apolipoprotein E and haptoglobin as DEGs, with a fold change about +2 and −2, in calcified femoral artery vs healthy artery, respectively, and clusterin and alpha-2-macroglobulin as close interactors that matched in our proteomic analysis. However, further studies are needed to elucidate the specific role of these proteins, and to evaluate its function as biomarkers or therapeutic targets. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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12 pages, 862 KiB

Open AccessArticle

Carotid Arterial Stiffness and Cardiometabolic Profiles in Women with Fibromyalgia

by Yunkyung Kim, Geun-Tae Kim and Jihun Kang

Biomedicines 2021, 9(12), 1786; https://doi.org/10.3390/biomedicines9121786 - 28 Nov 2021

Cited by 6 | Viewed by 2140

Abstract

Background: The present study aimed to evaluate the association between FM and cardiometabolic risk factors and carotid arterial stiffness in FM patients. Methods: The cardiometabolic risk profile was defined based on the Adult Treatment Panel III panel. Carotid intimal media thickness (cIMT) and arterial stiffness were assessed using high-resolution ultrasonography. Multivariate logistic analysis was performed to estimate the association between FM and cardiometabolic risk factors. We used a general linear regression to compare the cIMT and carotid beta-index between the participants with and without FM. Pearson’s coefficient was calculated to evaluate the potential correlation between cardiometabolic risk profiles, cIMT, and arterial stiffening in FM. Results: FM participants showed a higher risk of central obesity (odds ratio [OR] = 3.21, 95% confidence interval [CI] 1.49, 6.91), high triglyceride (OR = 4.73, 95% CI 2.29, 9.79), and impaired fasting glucose (IFG) (OR = 4.27, 95% CI 2.07, 8.81) compared to the control group. The FM group exhibited higher beta-index values than the control group (p = 0.003). Although IFG and triglyceride glucose index showed a tendency to correlate with the beta-index, statistical significance was not observed. Conclusions: FM was associated with an increased risk of central obesity, high triglyceride levels, and IFG. Furthermore, advanced arterial stiffness of the carotid artery was observed in FM, which might be correlated with insulin resistance. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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9 pages, 1432 KiB

Open AccessArticle

Perfusion Patterns in Patients with Chronic Limb-Threatening Ischemia versus Control Patients Using Near-Infrared Fluorescence Imaging with Indocyanine Green

by Pim Van Den Hoven, Lauren N. Goncalves, Paulus H. A. Quax, Catharina S. P. Van Rijswijk, Jan Van Schaik, Abbey Schepers, Alexander L. Vahrmeijer, Jaap F. Hamming and Joost R. Van Der Vorst

Biomedicines 2021, 9(10), 1417; https://doi.org/10.3390/biomedicines9101417 - 9 Oct 2021

Cited by 6 | Viewed by 2586

Abstract

In assessing the severity of lower extremity arterial disease (LEAD), physicians rely on clinical judgements supported by conventional measurements of macrovascular blood flow. However, current diagnostic techniques provide no information about regional tissue perfusion and are of limited value in patients with chronic limb-threatening ischemia (CLTI). Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been used extensively in perfusion studies and is a possible modality for tissue perfusion measurement in patients with CLTI. In this prospective cohort study, ICG NIR fluorescence imaging was performed in patients with CLTI and control patients using the Quest Spectrum Platform^® (Middenmeer, The Netherlands). The time–intensity curves were analyzed using the Quest Research Framework. Fourteen parameters were extracted. Successful ICG NIR fluorescence imaging was performed in 19 patients with CLTI and in 16 control patients. The time to maximum intensity (seconds) was lower for CLTI patients (90.5 vs. 143.3, p = 0.002). For the inflow parameters, the maximum slope, the normalized maximum slope and the ingress rate were all significantly higher in the CLTI group. The inflow parameters observed in patients with CLTI were superior to the control group. Possible explanations for the increased inflow include damage to the regulatory mechanisms of the microcirculation, arterial stiffness, and transcapillary leakage. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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11 pages, 1148 KiB

Open AccessArticle

Heart-Ankle Pulse Wave Velocity Is Superior to Brachial-Ankle Pulse Wave Velocity in Detecting Aldosterone-Induced Arterial Stiffness

by Zheng-Wei Chen, Chien-Ting Pan, Cheng-Hsuan Tsai, Yi-Yao Chang, Chin-Chen Chang, Bo-Ching Lee, Yu-Wei Chiu, Wei-Chieh Huang, Yu-Li Lin, Vin-Cent Wu, Chi-Sheng Hung, Che-Wei Liao, Yen-Hung Lin and on behalf of TAIPAI Study Group

Biomedicines 2021, 9(10), 1285; https://doi.org/10.3390/biomedicines9101285 - 22 Sep 2021

Cited by 6 | Viewed by 2544

Abstract

Primary aldosteronism (PA) is associated with higher arterial stiffness compared to essential hypertension (EH). However, few studies have compared different pulse wave velocity (PWV) parameters to detect aldosterone-induced arterial stiffness. In this study, we aimed to compare the sensitivity in detecting aldosterone-induced arterial stiffness between brachial-ankle PWV (baPWV) and heart-ankle PWV (haPWV). We prospectively enrolled 1006 PA patients and 983 EH patients. Detailed medical history, basic biochemistry data and two PWV measurements (baPWV and haPWV) were collected in both groups. We performed analysis on the original cohort and two propensity score matching (PSM) models (model 1 adjusted for age and sex; model 2 adjusted for age, sex, systolic and diastolic blood pressure). The DeLong test was used to compare areas under receiver operating characteristic curves (AUCs) between baPWV and haPWV to predict PA. In all models, the PA patients had significantly higher baPWV compared to the EH patients. The AUC of haPWV was greater than that of baPWV. In conclusion, haPWV seems to be a better PWV parameter than baPWV in detecting aldosterone-induced arterial stiffness. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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15 pages, 1885 KiB

Open AccessArticle

Glycomacropeptide for Management of Insulin Resistance and Liver Metabolic Perturbations

by Mathilde Foisy Sauvé, Francis Feldman, Mireille Koudoufio, Nour-El-Houda Ould-Chikh, Lena Ahmarani, Alain Sane, Thierry N’Timbane, Ramy El-Jalbout, Nathalie Patey, Schohraya Spahis, Alain Stintzi, Edgard Delvin and Emile Levy

Biomedicines 2021, 9(9), 1140; https://doi.org/10.3390/biomedicines9091140 - 2 Sep 2021

Cited by 9 | Viewed by 3474

Abstract

Background and Aims: The increasing prevalence and absence of effective global treatment for metabolic syndrome (MetS) are alarming given the potential progression to severe non-communicable disorders such as type 2 diabetes and nonalcoholic fatty liver disease. The purpose of this study was to investigate the regulatory role of glycomacropeptide (GMP), a powerful milk peptide, in insulin resistance and liver dysmetabolism, two central MetS conditions. Materials and Methods: C57BL/6 male mice were fed a chow (Ctrl), high-fat, high-sucrose (HFHS) diet or HFHS diet along with GMP (200 mg/kg/day) administered by gavage for 12 weeks. Results: GMP lowered plasma insulin levels (in response to oral glucose tolerance test) and HOMA-IR index, indicating a more elevated systemic insulin sensitivity. GMP was also able to decrease oxidative stress and inflammation in the circulation as reflected by the decline of malondialdehyde, F2 isoprostanes and lipopolysaccharide. In the liver, GMP raised the protein expression of the endogenous anti-oxidative enzyme GPx involving the NRF2 signaling pathway. Moreover, the administration of GMP reduced the gene expression of hepatic pro-inflammatory COX-2, TNF-α and IL-6 via inactivation of the TLR4/NF-κB signaling pathway. Finally, GMP improved hepatic insulin sensitization given the modulation of AKT, p38 MAPK and SAPK/JNK activities, thereby restoring liver homeostasis as revealed by enhanced fatty acid β-oxidation, reduced lipogenesis and gluconeogenesis. Conclusions: Our study provides evidence that GMP represents a promising dietary nutraceutical in view of its beneficial regulation of systemic insulin resistance and hepatic insulin signaling pathway, likely via its powerful antioxidant and anti-inflammatory properties. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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12 pages, 1656 KiB

Open AccessArticle

Variable Changes of Circulating ANGPTL3 and ANGPTL4 in Different Obese Phenotypes: Relationship with Vasodilator Dysfunction

by Francesca Schinzari, Giuseppina Vizioli, Umberto Campia, Manfredi Tesauro and Carmine Cardillo

Biomedicines 2021, 9(8), 1037; https://doi.org/10.3390/biomedicines9081037 - 18 Aug 2021

Cited by 8 | Viewed by 3186

Abstract

Obesity associates with premature atherosclerosis and an increased burden of cardiovascular disease, especially when accompanied by abnormalities of lipid and glucose metabolism. Angiopoietin-like (ANGPTL)3 and ANGPTL4 are metabolic regulators, whose upregulation is associated with dyslipidemia, insulin resistance and atherosclerosis. We analyzed, therefore, changes in circulating ANGPTL3 and ANGPTL4 in obese patients with different metabolic phenotypes and their relation with impaired vasodilator reactivity, an early abnormality in atherosclerosis. Compared to the lean subjects (n = 42), circulating ANGPTL3 was elevated (both p > 0.001) in the patients with metabolically unhealthy obesity (MUO; n = 87) and type 2 diabetes (T2D; n = 31), but not in those with metabolically healthy obesity (MHO; n = 48, p > 0.05). Circulating ANGPTL4, by contrast, was increased in all obese subgroups (all p < 0.001 vs. lean subjects). Vasodilator responses to both acetylcholine and sodium nitroprusside were reduced in the three obese subgroups vs. lean subjects (all p < 0.001), with greater impairment in the patients with T2D than in those with MHO and MUO (all p < 0.05). In the whole population, an inverse relationship (r = 0.27; p = 0.003) was observed between circulating ANGPTL4 and endothelium-dependent vasorelaxation. Circulating ANGPTL3 and ANGPTL4 undergo variable changes in obese patients with different metabolic phenotypes; changes in ANGPTL4 relate to endothelial dysfunction, making this protein a possible target for vascular prevention in these patients. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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14 pages, 1079 KiB

Open AccessArticle

The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study

by Gualtiero I. Colombo, Vanessa Bianconi, Alice Bonomi, Sara Simonelli, Mauro Amato, Beatrice Frigerio, Alessio Ravani, Cecilia Vitali, Daniela Sansaro, Daniela Coggi, Massimo R. Mannarino, Kai P. Savonen, Sudhir Kurl, Bruna Gigante, Andries J. Smit, Philippe Giral, Elena Tremoli, Laura Calabresi, Fabrizio Veglia, Matteo Pirro, Damiano Baldassarre and on behalf of the IMPROVE Study Group Show full author list Hide full author list

Biomedicines 2021, 9(3), 286; https://doi.org/10.3390/biomedicines9030286 - 11 Mar 2021

Cited by 8 | Viewed by 2537

Abstract

The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMT_max; cIMT_mean–max of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMT_mean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMT_max and cIMT_mean–max, but not with PF CC-IMT_mean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMT_max or cIMT_mean–max were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMT_max and cIMT_mean–max when the CETP concentration was below the median (HDL-C × CETP interaction, p = 0.001 and p = 0.003 for cIMT_max and cIMT_mean–max, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMT_max. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMT_max. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMT_max. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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Review

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25 pages, 964 KiB

Open AccessReview

Off-Target Effects of Antidepressants on Vascular Function and Structure

by Anna Dimoula, Dimitrios Fotellis, Evmorfia Aivalioti, Dimitrios Delialis, Alexia Polissidis, Raphael Patras, Nikolaos Kokras and Kimon Stamatelopoulos

Biomedicines 2022, 10(1), 56; https://doi.org/10.3390/biomedicines10010056 - 28 Dec 2021

Cited by 5 | Viewed by 4632

Abstract

Depression emerges as a risk factor for cardiovascular disease, and it is thought that successful antidepressant treatment may reduce such a risk. Therefore, antidepressant treatment embodies a potential preventive measure to reduce cardiovascular events in patients with depression. Accumulating evidence indicates that antidepressants have off-target effects on vascular dysfunction and in the early stages of atherosclerosis, which form the basis for cardiovascular disease (CVD) pathogenesis. In this context, we performed a thorough review of the evidence pertaining to the effects of different classes of antidepressant medications on hemodynamic and early atherosclerosis markers. The preclinical and clinical evidence reviewed revealed a preponderance of studies assessing selective serotonin reuptake inhibitors (SSRI), whereas other classes of antidepressants are less well-studied. Sufficient evidence supports a beneficial effect of SSRIs on vascular inflammation, endothelial function, arterial stiffening, and possibly delaying carotid atherosclerosis. In clinical studies, dissecting the hypothesized direct beneficial antidepressant effect of SSRIs on endothelial health from the global improvement upon remission of depression has proven to be difficult. However, preclinical studies armed with appropriate control groups provide evidence of molecular mechanisms linked to endothelial function that are indeed modulated by antidepressants. This suggests at least a partial direct action on vascular integrity. Further research on endothelial markers should focus on the effect of antidepressants on treatment responders versus non-responders in order to better ascertain the possible beneficial vascular effects of antidepressants, irrespective of the underlying course of depression. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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20 pages, 2423 KiB

Open AccessReview

Anatomy, Pathophysiology, Molecular Mechanisms, and Clinical Management of Erectile Dysfunction in Patients Affected by Coronary Artery Disease: A Review

by Giuseppe Sangiorgi, Alberto Cereda, Daniela Benedetto, Michela Bonanni, Gaetano Chiricolo, Linda Cota, Eugenio Martuscelli and Francesco Greco

Biomedicines 2021, 9(4), 432; https://doi.org/10.3390/biomedicines9040432 - 16 Apr 2021

Cited by 35 | Viewed by 15179

Abstract

Erectile dysfunction (ED) has been defined as the inability to attain or maintain penile erection sufficient for successful sexual intercourse. ED carries a notable influence on life quality, with significant implications for family and social relationships. Because atherosclerosis of penile arteries represents one of the most frequent ED causes, patients presenting with it should always be investigated for potential coexistent coronary or peripheral disease. Up to 75% of ED patients have a stenosis of the iliac-pudendal-penile arteries, supplying the male genital organ’s perfusion. Recently, pathophysiology and molecular basis of male erection have been elucidated, giving the ground to pharmacological and mechanical revascularization treatment of this condition. This review will focus on the normal anatomy and physiology of erection, the pathophysiology of ED, the relation between ED and cardiovascular diseases, and, lastly, on the molecular basis of erectile dysfunction. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases)

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