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Biomedicines
Special Issues
Circulating Pro- and Anti-angiogenic Factors in Cardiovascular Disorders
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Circulating Pro- and Anti-angiogenic Factors in Cardiovascular Disorders

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

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 11787

Special Issue Editor

Dr. Paweł Maga

E-Mail Website
Guest Editor
Department of Angiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland
Interests: vascular medicine; endothelium dysfunction; microcirculation; leukotrienes; angiogenesis; endovascular treatment; thrombosis

Special Issue Information

Dear Colleagues,

Angiogenesis is a process strictly regulated and modulated by the microenvironment and multiple pro- and antiangiogenic factors. Proper angiogenesis is the result of the balance between factors inducing and inhibiting it. The disturbance in this equipoise may lead to life-threatening vascular-related diseases influencing patients' life quality. An increasingly better understanding of angiogenesis and the factors affecting this process leads to the development of new, personalized therapies focused on ischemic diseases as well as those related to overintense angiogenesis, such as rheumatoid arthritis, psoriasis or neoplasms. In the last decade, therapeutic angiogenesis is gathering more and more scientific attention in the field of ischemic tissue treatment due to the stimulation of new vascular vessel creation based on existing vascular systems.

As cardiovascular diseases (CVDs) and their complications remain the leading cause of morbidity and death, especially in developed countries, the need for new and effective methods for their diagnosis, early detection, prognosis as well as the prediction of response to treatment is high. Among the multiple CVD biomarkers, the pro- and anti-angiogenic factors are still controversially seen as the parameters that could be used as reliable diagnostic and predicting tools in daily practice. This Special Issue of the Biomedicines journal focuses on the latest advances in the discovery, development and clinical applications of pro- and anti-angiogenic factors as clinical targets in cardiovascular disorders.

In this Special Issue, in vitro and in vivo studies, original research and reviews are all welcome.

Dr. Paweł Maga
Guest Editor

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Keywords

  • circulating angiogenic factors
  • biomarkers
  • peripheral vascular disease
  • atherosclerosis
  • diabetes foot
  • cardiovascular diseases
  • myocardial infarction
  • precision medicine
  • therapeutic angiogenesis
  • vascular signaling

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Published Papers (6 papers)

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Research

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18 pages, 2881 KiB  
Article
The Relationship between TNF-a, IL-35, VEGF and Cutaneous Microvascular Dysfunction in Young Patients with Uncomplicated Type 1 Diabetes
by Jolanta Neubauer-Geryk, Melanie Wielicka, Małgorzata Myśliwiec, Katarzyna Zorena and Leszek Bieniaszewski
Biomedicines 2023, 11(10), 2857; https://doi.org/10.3390/biomedicines11102857 - 22 Oct 2023
Cited by 4 | Viewed by 1539
Abstract
The aim of this study was to analyze the relationship between immunological markers and the dysfunction of cutaneous microcirculation in young patients with type 1 diabetes. The study group consisted of 46 young patients with type 1 diabetes and no associated complications. Microvascular [...] Read more.
The aim of this study was to analyze the relationship between immunological markers and the dysfunction of cutaneous microcirculation in young patients with type 1 diabetes. The study group consisted of 46 young patients with type 1 diabetes and no associated complications. Microvascular function was assessed with the use of nail fold capillaroscopy before and after implementing post-occlusive reactive hyperemia. This evaluation was then repeated after 12 months. Patients were divided into two subgroups according to their baseline median coverage (defined as the ratio of capillary surface area to surface area of the image area), which was established during the initial exam (coverageBASE). Additionally, the levels of several serum biomarkers, including VEGF, TNF-a and IL-35, were assessed at the time of the initial examination. HbA1c levels obtained at baseline and after a 12-month interval were also obtained. Mean HbA1c levels obtained during the first two years of the course of the disease were also analyzed. Patients with coverageBASE below 16.85% were found to have higher levels of VEGF and TNF-α, as well as higher levels of HbA1c during the first two years following diabetes diagnosis. Our results support the hypothesis that the development of diabetic complications is strongly influenced by metabolic memory and an imbalance of pro- and anti-inflammatory cytokines, regardless of achieving adequate glycemic control. Full article
(This article belongs to the Special Issue Circulating Pro- and Anti-angiogenic Factors in Cardiovascular Disorders)
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14 pages, 580 KiB  
Article
Angiogenin Levels and Carotid Intima-Media Thickness in Patients with Type 1 Diabetes and Metabolic Syndrome
by Jolanta Neubauer-Geryk, Melanie Wielicka, Grzegorz M. Kozera and Leszek Bieniaszewski
Biomedicines 2023, 11(9), 2591; https://doi.org/10.3390/biomedicines11092591 - 21 Sep 2023
Viewed by 1102
Abstract
It is well documented that in patients with type 1 diabetes (DM1), decreased levels of angiogenin are associated with the development of overt nephropathy. However, little is known about angiogenin levels and subclinical macrovascular organ damage in patients with DM1 and concomitant metabolic [...] Read more.
It is well documented that in patients with type 1 diabetes (DM1), decreased levels of angiogenin are associated with the development of overt nephropathy. However, little is known about angiogenin levels and subclinical macrovascular organ damage in patients with DM1 and concomitant metabolic syndrome (MS). Therefore, we analyzed the relationship between angiogenin levels and carotid intima-media thickness (cIMT) in DM1 patients with and without MS. We found that angiogenin concentration was significantly lower in DM1 patients compared to controls, while the cIMT measurements were comparable. Exclusion of patients with MS, patients with hypertension, undergoing treatment, or cigarette smokers did not change these findings. Of note, when comparing the subgroups of DM1 patients with and without MS, there was no significant difference between angiogenin levels. However, we did note a significant difference in these levels after the exclusion of smokers. The comparison of cIMT in these subgroups showed a significant difference between the study subgroups. This difference was no longer observed when the age of the patients was taken into account. In summary, it can be concluded that metabolic syndrome in patients with type 1 diabetes does not appear to impact angiogenin levels or cIMT. Full article
(This article belongs to the Special Issue Circulating Pro- and Anti-angiogenic Factors in Cardiovascular Disorders)
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12 pages, 505 KiB  
Article
The Concentration of Pro- and Antiangiogenic Factors in Saliva and Gingival Crevicular Fluid Compared to Plasma in Patients with Peripheral Artery Disease and Type 2 Diabetes
by Iwona Gregorczyk-Maga, Aleksandra Szustkiewicz-Karoń, Mateusz Gajda, Maria Kapusta, Wojciech Maga and Martyna Schönborn
Biomedicines 2023, 11(6), 1596; https://doi.org/10.3390/biomedicines11061596 - 31 May 2023
Cited by 2 | Viewed by 1518
Abstract
Several studies have investigated various biomarkers in relation to peripheral artery disease (PAD) for disease stratification and early-onset detection. In PAD, angiogenesis is required for tissue restoration and tissue perfusion. Considering changes in angiogenesis in patients with PAD, angiogenic factors could be explored [...] Read more.
Several studies have investigated various biomarkers in relation to peripheral artery disease (PAD) for disease stratification and early-onset detection. In PAD, angiogenesis is required for tissue restoration and tissue perfusion. Considering changes in angiogenesis in patients with PAD, angiogenic factors could be explored as one of the new prognostic molecules. In recent studies, saliva and gingival crevicular fluid (GCF) have gained recognition as new, easily obtained diagnostic materials. This study aimed to compare the levels of selected circulating angiogenic factors (VEGF-A, PDGF-BB, and ANG-1) in unstimulated whole saliva (WS) and GCF versus plasma at three points in time to find possible correlations between their concentrations among patients with PAD and diabetes type 2 in 32 patients with Rutherford stages 5 and 6. A significant positive correlation has been demonstrated between circulating PDGF-BB levels in GCF and plasma. In most cases, comorbidities do not have an impact on the change in general correlation for the whole group. Our results clearly showed that GCF could be a good source for PDGF assessment. However, future studies with a larger number of subjects are warranted to confirm this finding and identify the most accurate angiogenic biomarkers in saliva or GCF that could be applied in clinical practice. Full article
(This article belongs to the Special Issue Circulating Pro- and Anti-angiogenic Factors in Cardiovascular Disorders)
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20 pages, 6587 KiB  
Article
Circulating Angiogenic Factors and Ischemic Diabetic Foot Syndrome Advancement—A Pilot Study
by Martyna Schönborn, Iwona Gregorczyk-Maga, Krzysztof Batko, Katarzyna Bogucka, Mikołaj Maga, Anna Płotek, Patrycja Pasieka, Krystyna Słowińska-Solnica and Paweł Maga
Biomedicines 2023, 11(6), 1559; https://doi.org/10.3390/biomedicines11061559 - 27 May 2023
Cited by 3 | Viewed by 1569
Abstract
Despite clear evidence of inadequate angiogenesis in ischemic diabetic foot syndrome (DFS) pathogenesis, angiogenic factor level changes in patients with ischemic DFS remain inconsistent. This study aimed to assess circulating angiogenic factors concerning ischemic DFS advancement and describe their relationships with patients’ clinical [...] Read more.
Despite clear evidence of inadequate angiogenesis in ischemic diabetic foot syndrome (DFS) pathogenesis, angiogenic factor level changes in patients with ischemic DFS remain inconsistent. This study aimed to assess circulating angiogenic factors concerning ischemic DFS advancement and describe their relationships with patients’ clinical characteristics, microvascular parameters, and diabetic control. The study included 41 patients with ischemic DFS (67.3 (8.84) years; 82.9% males). Angiogenic processes were assessed by identifying circulating concentrations of five pro- and two anti-angiogenic factors. We found that penetrating ulcers were related to a significantly higher FGF-2 level (8.86 (5.29) vs. 5.23 (4.17) pg/mL, p = 0.02). Moreover, plasma FGF-2 showed a significant correlation with the SINBAD score (r = 0.32, p = 0.04), platelet count (r = 0.43, p < 0.01), white cell count (r = 0.42, p < 0.01), and age (r = −0.35, p = 0.03). We did not observe any significant linear relationship between the studied biomarkers and microcirculatory parameters, nor for glycemic control. In a univariate analysis using logistic regression, an increase in plasma FGF-2 was tied to greater odds of high-grade ulcers (OR 1.16; 95% CI 1.02–1.38, p = 0.043). This suggests that circulating FGF-2 may serve as a potential biomarker for predicting DFU advancement and progression. It is necessary to conduct further studies with follow-up observations to confirm this hypothesis. Full article
(This article belongs to the Special Issue Circulating Pro- and Anti-angiogenic Factors in Cardiovascular Disorders)
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Review

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13 pages, 658 KiB  
Review
Role of Epicardial Adipose Tissue Secretome on Cardiovascular Diseases
by Sara Leo, Elena Tremoli, Letizia Ferroni and Barbara Zavan
Biomedicines 2023, 11(6), 1653; https://doi.org/10.3390/biomedicines11061653 - 7 Jun 2023
Cited by 2 | Viewed by 1937
Abstract
Obesity and insulin resistance are associated with the inflamed and defective adipose tissue (AT) phenotype, and are established risk factors for cardiovascular diseases (CVDs). Extracellular vesicles (EVs) are a heterogeneous group of cell-derived lipid membrane vesicles involved in the onset and development of [...] Read more.
Obesity and insulin resistance are associated with the inflamed and defective adipose tissue (AT) phenotype, and are established risk factors for cardiovascular diseases (CVDs). Extracellular vesicles (EVs) are a heterogeneous group of cell-derived lipid membrane vesicles involved in the onset and development of many pathologies, including insulin resistance, diabetes, and CVDs. The inflammation associated with overweight and obesity triggers the transition of the AT secretome from healthy to pathological, with a consequent increased expression of pro-inflammatory mediators. Epicardial adipose tissue (EAT) is a specialized fat depot that surrounds the heart, in direct contact with the myocardium. Recently, the role of EAT in regulating the physiopathology of many heart diseases has been increasingly explored. In particular, the EAT phenotype and derived EVs have been associated with the onset and exacerbation of CVDs. In this review, we will focus on the role of the AT secretome in the case of CVDs, and will discuss the beneficial effects of EVs released by AT as promising therapeutic candidates. Full article
(This article belongs to the Special Issue Circulating Pro- and Anti-angiogenic Factors in Cardiovascular Disorders)
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Other

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19 pages, 1464 KiB  
Systematic Review
Impact of Blood-Flow-Restricted Training on Arterial Functions and Angiogenesis—A Systematic Review with Meta-Analysis
by Mikołaj Maga, Agnieszka Wachsmann-Maga, Krzysztof Batko, Aleksandra Włodarczyk, Paulina Kłapacz, Jakub Krężel, Natalia Szopa and Agnieszka Sliwka
Biomedicines 2023, 11(6), 1601; https://doi.org/10.3390/biomedicines11061601 - 31 May 2023
Cited by 3 | Viewed by 3343
Abstract
Despite growing evidence of the significant influence of blood-flow-restricted (BFR) training on different body functions, its impact on the vascular system, especially the arteries, is controversial. Therefore, the objective of our study was to analyze how BFR exercise, compared to other types of [...] Read more.
Despite growing evidence of the significant influence of blood-flow-restricted (BFR) training on different body functions, its impact on the vascular system, especially the arteries, is controversial. Therefore, the objective of our study was to analyze how BFR exercise, compared to other types of exercise without the restriction of blood flow, influences arterial functions and angiogenesis in adults. Studies comparing the effect of BFR versus non-BFR training on arterial parameters were divided into three categories: endothelial function, angiogenesis, and other vasculature functions. The search was based on Cochrane Library, PubMed®, and Embase, and 38 studies were included. The meta-analysis revealed a more significant improvement in flow-mediated dilatation (FMD) (p = 0.002) and the production of the primary angiogenesis biomarker vascular endothelial growth factor (VEGF) (p = 0.009) after BFR compared to non-BFR training (p = 0.002). The analysis of the pulse wave velocity, ankle-brachial index, systolic blood pressure, and heart rate did not show significant differences in changes between BFR and non-BFR training. The other parameters examined did not have sufficient data to be included in the meta-analysis. The results obtained present trends that suggest significant impacts of BFR training on endothelial functions and angiogenesis. There is still a lack of multicenter randomized clinical trials including many participants, and such studies are necessary to confirm the advantage of BFR over non-BFR activity. Full article
(This article belongs to the Special Issue Circulating Pro- and Anti-angiogenic Factors in Cardiovascular Disorders)
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