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Angiogenesis and Related Disorders

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

Deadline for manuscript submissions: 31 January 2025 | Viewed by 3884

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Dr. Jian Li

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Center for Molecular and Translational Medicine, Georgia State University, 157 Decatur Street, SE, Atlanta, GA 30303, USA
Interests: vascular biology; cardiovascular disease; metabolic diseases; evaluation of bioactive agents from natural sources
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Special Issue Information

Dear Colleagues,

Angiogenesis is a complex biological process that involves the formation of new blood vessels from existing ones, which is crucial for normal development and wound healing. Pathological angiogenesis, however, contributes to many diseases, particularly cardiovascular diseases (such as atherosclerosis, stroke, pulmonary hypertension, and cardiac hypertrophy), cancer, diabetic retinopathy, and diabetic delayed wound healing. Understanding the role of angiogenesis in these disorders is essential for developing _targeted therapies and improving patient outcomes.

While extensive research has been conducted on angiogenesis, this Special Issue aims to focus specifically on the translational aspects of angiogenesis research. We aim to provide a comprehensive understanding of angiogenesis and its relevance to specific disorders, in order to facilitate the development of _targeted therapies, diagnostic tools, and treatment interventions that can improve patient outcomes.

We welcome your contributions in the form of original research and review articles on aspects including, but not limited to, the following:

Therapeutic _target Identification: Identifying and understanding the molecular mechanisms that regulate angiogenesis in related disorders.
Biomarker Discovery: Identifying biomarkers that can be used to diagnose, prognose, and monitor angiogenesis and related disorders.
Drug Development and Preclinical Studies: Development and testing of novel or classical/clinical drugs and therapies _targeting angiogenesis in related disorders.
Clinical Implementation: Conducting clinical trials, optimizing treatment protocols, and developing guidelines for the management of angiogenesis and related disorders.

Dr. Jian Li
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

angiogenesis
cardiovascular diseases
cancers
diabetic complications
therapeutic _target
biomarkers
drug development
clinical implementation

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Published Papers (4 papers)

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Research

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15 pages, 8637 KiB

Open AccessArticle

SSL5-AnxA5 Fusion Protein Constructed Based on Human Atherosclerotic Plaque scRNA-Seq Data Preventing the Binding of Apoptotic Endothelial Cells, Platelets, and Inflammatory Cells

by Yifei Zhao, Xingyu He, Teng Hu, Tianli Xia, Fangyang Huang, Changming Li, Yiming Li, Fei Chen, Mao Chen, Jun Ma and Yong Peng

Biomedicines 2025, 13(1), 8; https://doi.org/10.3390/biomedicines13010008 - 24 Dec 2024

Viewed by 326

Abstract

Background and aims: Coronary obstruction following plaque rupture is a critical pathophysiological change in the progression of stable angina (SAP) to acute coronary syndrome (ACS). The accumulation of platelets and various inflammatory cells on apoptotic endothelial cells is a key factor in arterial obstruction after plaque rupture. Through single-cell sequencing analysis (scRNA-seq) of plaques from SAP and ACS patients, we identified significant changes in the annexin V and P-selectin glycoprotein ligand 1 pathways. Staphylococcal superantigen-like 5 (SSL5) is an optimal antagonist P-selectin glycoprotein ligand 1 (PSGL1), while annexin V (AnxA5) can precisely detect dead cells in vivo. We constructed the SSL5-AnxA5 fusion protein and observed its role in preventing the interaction between apoptotic endothelial cells, platelets, and inflammatory cells. Methods: The scRNA-seq data were extracted from the Gene Expression Omnibus (GEO) database. Single-cell transcriptome analysis results and cell–cell communication were analyzed to identify the ACS and SAP cell clusters and elucidate the intercellular communication differences. Then, we constructed and verified a fusion protein comprising SSL5 and AnxA5 domains via polymerase chain reaction (PCR) and Western blot. The binding capacity of the fusion protein to P-selectin and apoptotic cells was evaluated by flow cytometry and AnxA5-FITC apoptosis detection kit, respectively. Furthermore, co-incubation and immunofluorescence allowed us to describe the mediation effect of it between inflammatory cells and endothelial cells or activated platelets. Results: Our analysis of the scRNA-seq data showed that SELPLG (PSGL1 gene) and ANNEXIN had higher information flowing in ACS compared to SAP. The SELPLG signaling pathway network demonstrated a higher number of interactions in ACS, while the ANNEXIN signaling pathway network revealed stronger signaling from macrophages toward monocytes in ACS compared to SAP. Competition binding experiments with P-selectin showed that SSL5-AnxA5 induced a decrease in the affinity of PSGL1. SSL5-AnxA5 effectively inhibited the combination of endothelial cells with inflammatory cells and the interaction of activated platelets with inflammatory cells. Additionally, this fusion protein exhibited remarkable capability in binding to apoptotic cells. Conclusions: The bifunctional protein SSL5-AnxA5 exhibits promising potential as a protective agent against local inflammation in arterial tissues, making it an excellent candidate for PSGL1-related therapeutic interventions. Full article

(This article belongs to the Special Issue Angiogenesis and Related Disorders)

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17 pages, 10232 KiB

Open AccessArticle

Angiogenesis Dynamics: A Computational Model of Intravascular Flow Within a Structural Adaptive Vascular Network

by Sahar Jafari Nivlouei, Ana Guerra, Jorge Belinha, Naside Mangir, Sheila MacNeil, Christiane Salgado, Fernando Jorge Monteiro and Renato Natal Jorge

Biomedicines 2024, 12(12), 2845; https://doi.org/10.3390/biomedicines12122845 - 13 Dec 2024

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Abstract

Background: Understanding vascular development and the key factors involved in regulating angiogenesis—the growth of new blood vessels from pre-existing vasculature—is crucial for developing therapeutic approaches to promote wound healing. Computational techniques offer valuable insights into improving angiogenic strategies, leading to enhanced tissue regeneration and improved outcomes for chronic wound healing. While chorioallantoic membrane (CAM) models are widely used for examining fundamental mechanisms in vascular development, they lack quantification of essential parameters such as blood flow rate, intravascular pressure, and changes in vessel diameter. Methods: To address this limitation, the current study develops a novel two-dimensional mathematical model of angiogenesis, integrating discrete and continuous modelling approaches to capture intricate cellular interactions and provide detailed information about the capillary network’s structure. The proposed hybrid meshless-based model simulates sprouting angiogenesis using the in vivo CAM system. Results: The model successfully predicts the branching process with a total capillary volume fraction deviation of less than 15% compared to experimental data. Additionally, it implements blood flow through the capillary network and calculates the distribution of intravascular pressure and vessel wall shear stress. An adaptive network is introduced to consider capillary responses to hemodynamic and metabolic stimuli, reporting structural diameter changes across the generated vasculature network. The model demonstrates its robustness by verifying numerical outcomes, revealing statistically significant differences with deviations in key parameters, including diameter, wall shear stress (p < 0.05), circumferential wall stress, and metabolic stimuli (p < 0.01). Conclusion: With its strong predictive capability in simulating intravascular flow and its ability to provide both quantitative and qualitative assessments, this research enhances our understanding of angiogenesis by introducing a biologically relevant network that addresses the functional demands of the tissue. Full article

(This article belongs to the Special Issue Angiogenesis and Related Disorders)

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18 pages, 3595 KiB

Open AccessArticle

Pro-Inflammatory Characteristics of Extracellular Vesicles in the Vitreous of Type 2 Diabetic Patients

by Shengshuai Shan, Abdulaziz H. Alanazi, Yohan Han, Duo Zhang, Yutao Liu, S. Priya Narayanan and Payaningal R. Somanath

Biomedicines 2024, 12(9), 2053; https://doi.org/10.3390/biomedicines12092053 - 10 Sep 2024

Viewed by 1189

Abstract

Diabetic retinopathy (DR) is a leading cause of blindness, yet its molecular mechanisms are unclear. Extracellular vesicles (EVs) contribute to dysfunction in DR, but the characteristics and functions of vitreous EVs are unclear. This study investigated the inflammatory properties of type 2 diabetic (db) vitreous EVs. EVs isolated from the vitreous of db and non-db donors were used for nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), immunogold staining, Western blotting, and proteomic analysis by mass spectrometry. Intracellular uptake of vitreous EVs by differentiated macrophages was evaluated using ExoGlow membrane labeling, and the impact of EVs on macrophage (THP-1) activation was assessed by cytokine levels using RT-qPCR. NTA and TEM analysis of db and non-db vitreous EVs showed non-aggregated EVs with a heterogeneous size range below 200 nm. Western blot detected EV markers (Alix, Annexin V, HSP70, and Flotillin 1) and an upregulation of Cldn5 in db EVs. While the db EVs were incorporated into macrophages, treatment of THP-1 cells with db EVs significantly increased mRNA levels of TNFα and IL-1β compared to non-db EVs. Proteomic and gene enrichment analysis indicated pro-inflammatory characteristics of db EVs. Our results suggest a potential involvement of EC-derived Cldn5+ EVs in triggering inflammation, offering a novel mechanism involved and presenting a possible therapeutic avenue for DR. Full article

(This article belongs to the Special Issue Angiogenesis and Related Disorders)

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Review

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16 pages, 806 KiB

Open AccessReview

Angiogenesis of Avascular Necrosis of the Femoral Head: A Classic Treatment Strategy

by Ping Wang, Wenkai Shao, Yuxi Wang, Bo Wang, Xiao Lv and Yong Feng

Biomedicines 2024, 12(11), 2577; https://doi.org/10.3390/biomedicines12112577 - 11 Nov 2024

Viewed by 880

Abstract

Avascular necrosis of the femoral head (ANFH) is a type of osteonecrosis due to the cessation of blood supply, characterized by persistent local pain and collapse of the joint. The etiology of ANFH is multifaceted, and while its precise pathogenesis remains elusive, it is currently widely believed that the femoral head is highly dependent on the vascular system. A large number of studies have shown that vascular injury is the initial factor in the onset of ANFH. In this review, we briefly introduced the process of angiogenesis and the blood supply to the femoral head, with a focus on summarizing the existing research on promoting angiogenesis for the treatment of ANFH. We conclude that providing alternative pathways through angiogenesis to resolve the problem of the obstructed free flow of the blood is an important means of treating ANFH. Moreover, we also looked forward to the mechanism of endothelial metabolism, which has not yet been studied in femoral head necrosis models, providing potential strategies for more effective use of angiogenesis for the treatment of femoral head necrosis. Full article

(This article belongs to the Special Issue Angiogenesis and Related Disorders)

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