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Molecular Mechanisms of Angiogenesis in Health and Diseases 2.0
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Molecular Mechanisms of Angiogenesis in Health and Diseases 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 20294

Special Issue Editors

Prof. Dr. Miguel Ángel Medina Torres

E-Mail Website
Guest Editor
Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, E-29071 Málaga, Spain
Interests: angiogenesis; tumor metabolism; membrane transporters: plasma membrane redox; rare diseases; systems biology; polyamine and biogenic amine metabolism; metabolic modelling
Special Issues, Collections and Topics in MDPI journals
Dr. Adel Elmoselhi

E-Mail Website
Guest Editor
Basic Medical Sciences Department, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates
Interests: cardiovascular diseases; medical education; angiogenesis

Special Issue Information

Dear Colleagues,

Angiogenesis is an essential process for tissue survival, both physiologically during fetus development and wound healing, as well as pathologically in a plethora of diseases such as cancer, obesity, diabetic retinopathy, endometriosis, and skin and bone diseases. More recently, angiogenesis has also been shown to have an important role in tissue adaptation under microgravity and other space environments. The new capillaries that develop in angiogenesis sprout from existing vessels and are usually initiated via hypoxia and a lack of nutrients in the surrounding tissues. Angiogenesis is facilitated by pro-angiogenic factors such as VEGF and FGFs, among other mechanisms, and inhibited by anti-angiogenic factors. The therapeutic potential of regulating angiogenesis is tremendous since it is capable of treating major highly prevalent fatal diseases such as ischemic heart disease, stroke, and cancers. For this reason and others, the field of angiogenesis has been growing exponentially in the last fifty years; however, it is still far from reaching its potential. In this Special Issue, the aims are to provide an update on molecular mechanisms of angiogenesis relevant to various aspects in health and diseases, shed some light on the current development of angiogenesis-related diagnostic and therapeutic approaches, and to point out possible future directions.

Prof. Dr. Miguel Ángel Medina Torres
Dr. Adel Elmoselhi
Guest Editors

Manuscript Submission Information

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Keywords

  • angiogenesis
  • endothelial cells
  • vascular endothelial growth factors (VEGFs)
  • pro-angiogenic factors
  • anti-angiogenic factors
  • hypoxia
  • cancer
  • ischemic heart diseases
  • obesity
  • diabetic retinopathy

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Published Papers (6 papers)

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Research

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18 pages, 4971 KiB  
Article
The 14-Kilodalton Human Growth Hormone Fragment a Potent Inhibitor of Angiogenesis and Tumor Metastasis
by Baraah Tariq Shaker, Asmaa Anwar Ismail, Rawan Salih, Hassen Hadj Kacem, Mohamed Rahmani, Ingrid Struman and Khalid Bajou
Int. J. Mol. Sci. 2023, 24(10), 8877; https://doi.org/10.3390/ijms24108877 - 17 May 2023
Cited by 1 | Viewed by 2299
Abstract
The 14-kilodalton human growth hormone (14 kDa hGH) N-terminal fragment derived from the proteolytic cleavage of its full-length counterpart has been shown to sustain antiangiogenic potentials. This study investigated the antitumoral and antimetastatic effects of 14 kDa hGH on B16-F10 murine melanoma cells. [...] Read more.
The 14-kilodalton human growth hormone (14 kDa hGH) N-terminal fragment derived from the proteolytic cleavage of its full-length counterpart has been shown to sustain antiangiogenic potentials. This study investigated the antitumoral and antimetastatic effects of 14 kDa hGH on B16-F10 murine melanoma cells. B16-F10 murine melanoma cells transfected with 14 kDa hGH expression vectors showed a significant reduction in cellular proliferation and migration associated with an increase in cell apoptosis in vitro. In vivo, 14 kDa hGH mitigated tumor growth and metastasis of B16-F10 cells and was associated with a significant reduction in tumor angiogenesis. Similarly, 14 kDa hGH expression reduced human brain microvascular endothelial (HBME) cell proliferation, migration, and tube formation abilities and triggered apoptosis in vitro. The antiangiogenic effects of 14 kDa hGH on HBME cells were abolished when we stably downregulated plasminogen activator inhibitor-1 (PAI-1) expression in vitro. In this study, we showed the potential anticancer role of 14 kDa hGH, its ability to inhibit primary tumor growth and metastasis establishment, and the possible involvement of PAI-1 in promoting its antiangiogenic effects. Therefore, these results suggest that the 14 kDa hGH fragment can be used as a therapeutic molecule to inhibit angiogenesis and cancer progression. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Angiogenesis in Health and Diseases 2.0)
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12 pages, 2449 KiB  
Article
The Immunomodulator Dimethyl Itaconate Inhibits Several Key Steps of Angiogenesis in Cultured Endothelial Cells
by Isabel Vidal, Elena Fernández-Florido, Ana Dácil Marrero, Laura Castilla, Ana R. Quesada, Beatriz Martínez-Poveda and Miguel Ángel Medina
Int. J. Mol. Sci. 2022, 23(24), 15972; https://doi.org/10.3390/ijms232415972 - 15 Dec 2022
Cited by 3 | Viewed by 2251
Abstract
The dimethyl derivative of the immunomodulator itaconate has been previously shown to have anti-inflammatory, anti-oxidative, and immunomodulatory effects. In the present work, we evaluate the potential of dimethyl itaconate as an anti-angiogenic compound by using cultured endothelial cells and several in vitro assays [...] Read more.
The dimethyl derivative of the immunomodulator itaconate has been previously shown to have anti-inflammatory, anti-oxidative, and immunomodulatory effects. In the present work, we evaluate the potential of dimethyl itaconate as an anti-angiogenic compound by using cultured endothelial cells and several in vitro assays that simulate key steps of the angiogenic process, including endothelial cell proliferation, migration, invasion, and tube formation. Our results show that dimethyl itaconate interferes with all the previously mentioned steps of the angiogenic process, suggesting that dimethyl itaconate behaves as an anti-angiogenic compound. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Angiogenesis in Health and Diseases 2.0)
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Review

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14 pages, 1852 KiB  
Review
Perspectives for Improving the Tumor Targeting of Nanomedicine via the EPR Effect in Clinical Tumors
by Jinseong Kim, Hanhee Cho, Dong-Kwon Lim, Min Kyung Joo and Kwangmeyung Kim
Int. J. Mol. Sci. 2023, 24(12), 10082; https://doi.org/10.3390/ijms241210082 - 13 Jun 2023
Cited by 18 | Viewed by 2757
Abstract
Over the past few decades, the enhanced permeability and retention (EPR) effect of nanomedicine has been a crucial phenomenon in targeted cancer therapy. Specifically, understanding the EPR effect has been a significant aspect of delivering anticancer agents efficiently to targeted tumors. Although the [...] Read more.
Over the past few decades, the enhanced permeability and retention (EPR) effect of nanomedicine has been a crucial phenomenon in targeted cancer therapy. Specifically, understanding the EPR effect has been a significant aspect of delivering anticancer agents efficiently to targeted tumors. Although the therapeutic effect has been demonstrated in experimental models using mouse xenografts, the clinical translation of the EPR effect of nanomedicine faces several challenges due to dense extracellular matrix (ECM), high interstitial fluid pressure (IFP) levels, and other factors that arise from tumor heterogeneity and complexity. Therefore, understanding the mechanism of the EPR effect of nanomedicine in clinics is essential to overcome the hurdles of the clinical translation of nanomedicine. This paper introduces the basic mechanism of the EPR effect of nanomedicine, the recently discussed challenges of the EPR effect of nanomedicine, and various strategies of recent nanomedicine to overcome the limitations expected from the patients’ tumor microenvironments. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Angiogenesis in Health and Diseases 2.0)
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21 pages, 13753 KiB  
Review
Endometrial Angiogenesis of Abnormal Uterine Bleeding and Infertility in Patients with Uterine Fibroids—A Systematic Review
by Emma E. Don, Mei-An Middelkoop, Wouter J. K. Hehenkamp, Velja Mijatovic, Arjan W. Griffioen and Judith A. F. Huirne
Int. J. Mol. Sci. 2023, 24(8), 7011; https://doi.org/10.3390/ijms24087011 - 10 Apr 2023
Cited by 10 | Viewed by 4072
Abstract
Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated [...] Read more.
Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Angiogenesis in Health and Diseases 2.0)
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13 pages, 5019 KiB  
Review
An Altered Neurovascular System in Aging-Related Eye Diseases
by Yoon Kyung Choi
Int. J. Mol. Sci. 2022, 23(22), 14104; https://doi.org/10.3390/ijms232214104 - 15 Nov 2022
Cited by 3 | Viewed by 2014
Abstract
The eye has a complex and metabolically active neurovascular system. Repeated light injuries induce aging and trigger age-dependent eye diseases. Damage to blood vessels is related to the disruption of the blood-retinal barrier (BRB), altered cellular communication, disrupted mitochondrial functions, and exacerbated aggregated [...] Read more.
The eye has a complex and metabolically active neurovascular system. Repeated light injuries induce aging and trigger age-dependent eye diseases. Damage to blood vessels is related to the disruption of the blood-retinal barrier (BRB), altered cellular communication, disrupted mitochondrial functions, and exacerbated aggregated protein accumulation. Vascular complications, such as insufficient blood supply and BRB disruption, have been suggested to play a role in glaucoma, age-related macular degeneration (AMD), and Alzheimer’s disease (AD), resulting in neuronal cell death. Neuronal loss can induce vision loss. In this review, we discuss the importance of the neurovascular system in the eye, especially in aging-related diseases such as glaucoma, AMD, and AD. Beneficial molecular pathways to prevent or slow down retinal pathologic processes will also be discussed. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Angiogenesis in Health and Diseases 2.0)
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19 pages, 4398 KiB  
Review
Metabolic Reprogramming in Tumor Endothelial Cells
by Melissa García-Caballero, Liliana Sokol, Anne Cuypers and Peter Carmeliet
Int. J. Mol. Sci. 2022, 23(19), 11052; https://doi.org/10.3390/ijms231911052 - 21 Sep 2022
Cited by 24 | Viewed by 5886
Abstract
The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. [...] Read more.
The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. Recent advances have shown that tumor endothelial cell metabolism is reprogrammed, and that targeting endothelial metabolic pathways impacts developmental and pathological vessel sprouting. Therefore, the use of metabolic antiangiogenic therapies to normalize the blood vasculature, in combination with immunotherapies, offers a clinical niche to treat cancer. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Angiogenesis in Health and Diseases 2.0)
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