Understanding the Molecular Mechanisms of Angiogenesis

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 8335

Special Issue Editors

Unit of Experimental Oncology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Interests: FGF/FGFR system; tumor biology; tumor angiogenesis; molecular pathways in tumors; multiple myeloma; novel anti-cancer drugs; FGF trap small molecules
Unit of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Interests: mechanisms of tumorigenesis; cancer metabolism; tumor angiogenesis; receptor tyrosine kinases; novel anti-cancer agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Angiogenesis is a pivotal process involved in embryonic development and organ growth and repair. Pathological angiogenesis, resulting from an imbalance in the growth of blood vessels, characterizes various inflammatory, infectious, immune and malignant diseases. During angiogenesis, several cell types, soluble factors, and ECM components cooperate to orchestrate the growth of new blood vessels. Novel signaling pathways and players controlling pathological angiogenesis are continuously reported. However, many molecular mechanisms still remain poorly characterized. Thus, completing the picture is a major challenge for the future of angiogenesis research.

In recent years, intensive efforts have been dedicated to design drugs targeting aberrant angiogenesis in cancer and ocular diseases or promoting blood vessel growth for the re-vascularization of ischemic tissues. While promoting angiogenesis has been revealed to be more challenging, these efforts have led to the approval of various drugs that block angiogenesis and are in use for the treatment of blindness and cancer. However, anti-angiogenic medicines display poor efficacy in some contexts and resistance often occurs. Additionally, adverse effects limit the use of such drugs.

A deeper understanding of the molecular mechanisms driving angiogenesis is critical to develop effective treatments for human diseases driven by defects in blood vessel growth and to overcome the limitations of current approaches.

This Special Issue aims to summarize the current knowledge and cutting-edge research on the molecular mechanisms of angiogenesis. Reports can address both physiological and pathological angiogeneses. In the latter case, we ask authors to focus on potential new drug targets or therapeutic strategies. Translational studies are particularly welcome. We also encourage authors to present non-canonical views in opinion papers or reviews.

Dr. Arianna Giacomini
Dr. Elisabetta Grillo
Guest Editors

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. Cells is an international peer-reviewed open access semimonthly 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 2700 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
  • molecular pathways
  • anti/pro-angiogenic approaches
  • druggable targets

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

14 pages, 4147 KiB  
Article
590 nm LED Irradiation Improved Erythema through Inhibiting Angiogenesis of Human Microvascular Endothelial Cells and Ameliorated Pigmentation in Melasma
by Xiaoxi Dai, Shanglin Jin, Yijie Xuan, Yiwen Yang, Xiaoli Lu, Chen Wang, Li Chen, Leihong Xiang and Chengfeng Zhang
Cells 2022, 11(24), 3949; https://doi.org/10.3390/cells11243949 - 07 Dec 2022
Cited by 9 | Viewed by 2061
Abstract
Melasma is a common refractory acquired pigmentary skin disease that mainly affects middle-aged women. The pathogenesis of melasma is still uncertain, while abnormal vascular endothelial cells may play a role. We previously demonstrated the yellow light of light-emitting diodes (LED) could inhibit melanogenesis [...] Read more.
Melasma is a common refractory acquired pigmentary skin disease that mainly affects middle-aged women. The pathogenesis of melasma is still uncertain, while abnormal vascular endothelial cells may play a role. We previously demonstrated the yellow light of light-emitting diodes (LED) could inhibit melanogenesis through the photobiomodulation (PBM) of melanocytes and keratinocytes. In the current study, we investigated the effect of 590 nm LED on the function of human microvascular endothelial cells (HMEC-1). We revealed 0–40 J/cm2 590 nm LED had no toxic effect on HMEC-1 in vitro. 590 nm LED irradiation significantly reduced cell migration, tube formation, as well as the expression of vascular endothelial growth factor (VEGF) and stem cell factor (SCF), a pro-melanogenic factor. Moreover, we illustrated that 590 nm LED inhibited the phosphorylation of the AKT/PI3K/mTOR signaling pathway, and the inhibitory effect on HMEC-1 could be partially reversed by insulin-like growth factor 1 (IGF-1), an AKT/PI3K/mTOR pathway agonist. Besides, we conducted a pilot clinical study and observed a marked improvement on facial erythema and pigmentation in melasma patients after amber LED phototherapy. Taken together, 590 nm LED inhibited HMEC-1 migration, tube formation and the secretion of VEGF and SCF, predominantly through the inhibition of the AKT/PI3K/mTOR pathway, which may serve as a novel therapeutic option for melasma. Full article
(This article belongs to the Special Issue Understanding the Molecular Mechanisms of Angiogenesis)
Show Figures

Figure 1

26 pages, 5871 KiB  
Article
New Insight on 2D In Vitro Angiogenesis Models: All That Stretches Is Not a Tube
by Irina Beloglazova, Ekaterina Zubkova, Konstantin Dergilev, Yulia Goltseva and Yelena Parfyonova
Cells 2022, 11(20), 3278; https://doi.org/10.3390/cells11203278 - 18 Oct 2022
Cited by 2 | Viewed by 1824
Abstract
A Matrigel-based tube formation assay is a simple and widely accepted 2D angiogenesis model in vitro. Extracellular matrix (EM) proteins and growth factors (GFs) from MatrigelTM exclusively trigger endothelial cell (EC) tubular network (ETN) formation. Co-culture of ECs with mesenchymal stromal cells [...] Read more.
A Matrigel-based tube formation assay is a simple and widely accepted 2D angiogenesis model in vitro. Extracellular matrix (EM) proteins and growth factors (GFs) from MatrigelTM exclusively trigger endothelial cell (EC) tubular network (ETN) formation. Co-culture of ECs with mesenchymal stromal cells (MSCs) is another and more reliable in vitro angiogenesis assay. MSCs modulate ETN formation through intercellular interactions and as a supplier of EM and GFs. The aim of the present study was to compare the expression profile of ECs in both models. We revealed upregulation of the uPA, uPAR, Jagged1, and Notch2 genes in dividing/migrating ECs and for ECs in both experimental models at 19 h. The expression of endothelial–mesenchymal transition genes largely increased in co-cultured ECs whereas Notch and Hippo signaling pathway genes were upregulated in ECs on MatrigelTM. We showed that in the co-culture model, basement membrane (BM) deposition is limited only to cell-to-cell contacts in contrast to MatrigelTM, which represents by itself fully pre-assembled BM matrix. We suggest that ETN in a co-culture model is still in a dynamic process due to immature BM whereas ECs in the MatrigelTM assay seem to be at the final stage of ETN formation. Full article
(This article belongs to the Special Issue Understanding the Molecular Mechanisms of Angiogenesis)
Show Figures

Graphical abstract

21 pages, 4347 KiB  
Article
Targeting Anti-Angiogenic VEGF165b–VEGFR1 Signaling Promotes Nitric Oxide Independent Therapeutic Angiogenesis in Preclinical Peripheral Artery Disease Models
by Sivaraman Kuppuswamy, Brian H. Annex and Vijay C. Ganta
Cells 2022, 11(17), 2676; https://doi.org/10.3390/cells11172676 - 28 Aug 2022
Cited by 5 | Viewed by 1918
Abstract
Nitric oxide (NO) is the critical regulator of VEGFR2-induced angiogenesis. Neither VEGF-A over-expression nor L-Arginine (NO-precursor) supplementation has been effective in helping patients with Peripheral Artery Disease (PAD) in clinical trials. One incompletely studied reason may be due to the presence of the [...] Read more.
Nitric oxide (NO) is the critical regulator of VEGFR2-induced angiogenesis. Neither VEGF-A over-expression nor L-Arginine (NO-precursor) supplementation has been effective in helping patients with Peripheral Artery Disease (PAD) in clinical trials. One incompletely studied reason may be due to the presence of the less characterized anti-angiogenic VEGF-A (VEGF165b) isoform. We have recently shown that VEGF165b inhibits ischemic angiogenesis by blocking VEGFR1, not VEGFR2 activation. Here we wanted to determine whether VEGF165b inhibition using a monoclonal isoform-specific antibody against VEGF165b vs. control, improved perfusion recovery in preclinical PAD models that have impaired VEGFR2-NO signaling, including (1) type-2 diabetic model, (2) endothelial Nitric oxide synthase-knock out mice, and (3) Myoglobin transgenic mice that have impaired NO bioavailability. In all PAD models, VEGF165b inhibition vs. control enhanced perfusion recovery, increased microvascular density in the ischemic limb, and activated VEGFR1-STAT3 signaling. In vitro, VEGF165b inhibition vs. control enhanced a VEGFR1-dependent endothelial survival/proliferation and angiogenic capacity. These data demonstrate that VEGF165b inhibition induces VEGFR1-STAT3 activation, which does not require increased NO to induce therapeutic angiogenesis in PAD. These results may have implications for advancing therapies for patients with PAD where the VEGFR2-eNOS-NO pathway is impaired. Full article
(This article belongs to the Special Issue Understanding the Molecular Mechanisms of Angiogenesis)
Show Figures

Figure 1

10 pages, 3874 KiB  
Article
Hypertensive Stimuli Indirectly Stimulate Lymphangiogenesis through Immune Cell Secreted Factors
by Brooke K. Wilcox, Marissa R. Henley, Shobana Navaneethabalakrishnan, Karina A. Martinez, Anil Pournouri, Bethany L. Goodlett, Alexandra H. Lopez, Miranda L. Allbee, Emma J. Pickup, Kayla J. Bayless, Sanjukta Chakraborty and Brett M. Mitchell
Cells 2022, 11(14), 2139; https://doi.org/10.3390/cells11142139 - 07 Jul 2022
Cited by 1 | Viewed by 1757
Abstract
(1) Background: Renal immune cells and lymphatic vessel (LV) density have been reported previously to be increased in multiple mouse models of hypertension (HTN). However, whether interstitial levels of HTN stimuli such as angiotensin II, salt, or asymmetric dimethylarginine have a direct or [...] Read more.
(1) Background: Renal immune cells and lymphatic vessel (LV) density have been reported previously to be increased in multiple mouse models of hypertension (HTN). However, whether interstitial levels of HTN stimuli such as angiotensin II, salt, or asymmetric dimethylarginine have a direct or indirect effect on lymphangiogenesis is unknown. We hypothesized that these 3 HTN stimuli directly increase lymphatic endothelial cell (LEC) proliferation, LEC 3-D matrix invasion and vessel formation, and sprouting of mouse mesometrial LVs. (2) Methods: Human LECs (hLECs) and mouse LECs (mLECs) were treated with HTN stimuli while explanted mouse mesometrial LVs were treated with either the same HTN stimuli or with HTN stimuli-conditioned media. Conditioned media was prepared by treating murine splenocytes with HTN stimuli. (3) Results: HTN stimuli had no direct effect on hLEC or mLEC proliferation. Treatment of hLECs with HTN stimuli increased the number of lumen-forming structures and invasion distance (both p < 0.05) in the 3-D matrix but decreased the average lumen diameter and the number of cells per invading structure (both p < 0.05). Conditioned media from HTN-stimuli-treated splenocytes significantly attenuated the decrease in sprout number (aside from salt) and sprout length of mouse mesometrial LVs that is found in the HTN stimuli alone. (4) Conclusions: These data indicate that HTN stimuli indirectly prevent a decrease in lymphangiogenesis through secreted factors from HTN-stimuli-treated immune cells. Full article
(This article belongs to the Special Issue Understanding the Molecular Mechanisms of Angiogenesis)
Show Figures

Figure 1

Back to TopTop