Angiogenesis & VEGF

[Guide]

"Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over this, vasculogenesis is the term used for spontaneous bloodvessel formation, and intussusception is the term for new blood vessel formation by splitting off existing ones. Angiogenesis is a normal process in growth and development, as well as in wound healing. However, this is also a fundamental step in the transition of tumors from a dormant state to a malignant state. VEGF (Vascular Endothelial Growth Factor) has been demonstrated to be a major contributor to angiogenesis, increasing the number of capillaries in a given network." [1]

"Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis." Wikipedia

"Vascular endothelial growth factor (VEGF ) is an important signaling protein involved in both vasculogenesis (the de novo formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/macrophage migration, neurons, cancer cells, kidney epithelial cells). In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor." [2]

"Dr. Sandra Cremers, assistant professor of ophthalmology at Harvard Medical School, was awarded $25,000 for a study evaluating the role of angiogenesis (new blood vessel formation) in ocular rosacea. Dr. Cremers will investigate the levels of angiogenesis markers, such as vascular endothelial growth factor (VEGF ), in the conjunctiva and eyelids of patients with severe ocular rosacea, compared with normal subjects. She postulates that defining the role of angiogenesis in the development of ocular rosacea may bring focus to future research on this common rosacea subtype, and eventually lead to the development of an effective treatment." [3]

Dr. Cremers is a volunteer RRDi MAC member.

"Recently an increased of VEGF in Rosacea, a major mitogen for dermal microvascular endothelial cells is also reported." [4]

"VEGF, IL-2, IL-8 may be directly related to the mechanism of the development of cardiovascular disease in rosacea patients" [5]

"The principal subtype of rosacea includes erythematotelangiestatic rosacea, which is characterized by uncontrolled angiogenesis. Angiogenic growth factors such as fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) are currently targets of intense effort to inhibit deregulated blood vessel formation in diseases such as cancer. Here we report a 33-years-old woman with erythematotelangestatic rosacea who responds to a daily treatment of topically applied dobesilate, an inhibitor of FGF, with an improvement in erythema and telangectasia after two weeks. Thus, dobesilate might be useful in the treatment of rosacea and other diseases that depend on pathologic angiogenesis." [6]

"It should be also taken into account that, being FGF a necessary mediator of VEGF activity, dobesilate also inhibits this last signalling system, as it has been also recently described. The case report presented here is a representative example of five enrolled rosacea patients from a study directed to assess the long-term clinical benefit of dobesilate in rosacea. Taken together these data support a new therapeutic modality for a safe and efficient topical treatment of rosacea." [7]

"The present findings indicate that +405C/G polymorphism of the VEGF gene increases the risk of rosacea." [8]

"The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis.... Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea." [10]

Treatment

"ART ameliorated rosacea-like dermatitis by regulating immune response and angiogenesis, indicating that it could represent an effective therapeutic option for patients with rosacea." [9]

"Our results indicate that the blockade of YAP/TAZ contributes to anti-angiogenic responses in rosacea and VEGF-related angiogenesis. We suggest that YAP/TAZ can serve as a therapeutic target for rosacea and other inflammatory skin diseases associated with angiogenesis." [10]

"Besides, aspirin administration decreased the microvessels density and the VEGF expression in rosacea-like skin. We further demonstrated that aspirin inhibited the activation of NF-κB signaling and the release of its downstream pro-inflammatory cytokines." [11]

 

End Notes

[1] http://en.wikipedia....ki/Angiogenesis

[2] http://en.wikipedia.org/wiki/VEGF

[3] http://www.rosacea.o...arded/index.php

[4] New aspects of the pathogenesis of rosacea
Sabine Fimmel, Mohamed Badawy Abdel-Naser, Heinz Kutzner, Albert M. Kligman, Christos C. Zouboulis
Arch Dermatol Res, DOI 10.1007/s00403-007-0816-z, 5 June 2007, Revised 28 September 2007 / Accepted 19 November 2007, Springer - Verlag 2007 Full Text

[5] RISK-FACTORS OF CARDIOVASCULAR DISEASE IN PATIENTS WITH ROSACEA

[6] Eur J Med Res. 2005 Oct 18;10(10):454-6.
Therapeutic response of rosacea to dobesilate.
Cuevas P, Arrazola JM.

[7] BMJ Case Rep. 2011; 2011: bcr0820114579.
Published online 2011 Oct 19. doi:  10.1136/bcr.08.2011.4579
PMCID: PMC3207764
Long-term effectiveness of dobesilate in the treatment of papulopustular rosacea
Pedro Cuevas, Javier Angulo, and Guillermo Giménez-Gallego

[8] J Am Acad Dermatol. 2019 Jun 07;:
Vascular endothelial growth factor gene polymorphisms in patients with rosacea: A case-control study.
Hayran Y, Lay I, Mocan MC, Bozduman T, Ersoy-Evans S

[9] Biomedicine & Pharmacotherapy, Volume 117, September 2019, 109181
Artemisinin, a potential option to inhibit inflammation and angiogenesis in rosacea
XinYuana, Ji Li, Yangfan Li. Zhili Deng, Lei Zhou, Juan Long, Yan Tang. Zhihong Zuo, Yiya Zhang. Hongfu Xie

[10] Int J Mol Sci. 2021 Jan; 22(2): 931.
Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model
Jihyun Lee, Yujin Jung, Seo won Jeong, Ga Hee Jeong, Gue Tae Moon, and Miri Kim

[11] Aspirin alleviates skin inflammation and angiogenesis in rosacea

[Guide]

"VEGF, IL-2, IL-8 may be directly related to the mechanism of the development of cardiovascular disease in rosacea patients"

RISK-FSCTORS OF CARDIOVASCULAR DISEASE IN PATIENTS WITH ROSACEA.
Georgian Med News. 2017 Jan;(262):49-52
Tsiskarishvili T, Katsitadze A, Tsiskarishvili NI, Chigladze V

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"Recently, the role of vasoactive peptides has been increasingly discussed in the pathogenesis of rosacea. The most attention is paid to the growth factor of the vascular endothelium (VEGF). VEGF affects angiogenesis and survival of immature blood vessels."

Georgian Med News. 2018 Feb;(Issue):94-97.
[THE ROLE OF SOME VAZOACTIVE PEPTIDES IN THE PATHOGENESIS OF EARLY FORMES OF ROSACEA AND THE HEMOSTASIS SYSTEM].
Tsiskarishvili T1, Katsitadze A1, Tsiskarishvili NV1, Tsiskarishvili NI1.

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J Dermatol. 2017 Jul;44(7):836-837. doi: 10.1111/1346-8138.13665.
Identification of an epidermal marker for reddened skin: Vascular endothelial growth factor A.
Kajiya K1, Kajiya-Sawane M1, Ono T1, Sato K2.

"Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF)......We show evidence explaining the anti-inflammatory effect of Dermasence Refining Gel in rosacea pathogenesis in vitro. The adjunctive use of DRG in mild to moderate rosacea as a topical cosmetic seems medically reasonable."

J Cosmet Dermatol. 2017 Dec;16(4):e31-e36. doi: 10.1111/jocd.12323. Epub 2017 Mar 27.
Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.
Borelli C1, Becker B2, Thude S3, Fehrenbacher B1, Isermann D4.

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3.6. OS and Angiogenesis Associated with Rosacea

Rosacea is a common chronic inflammatory dermatosis, clinically characterized by erythema of the central face, episodic flushing, papules, and pustules. Skin care and pharmacologic treatments are the pillars of effective management of rosacea. Apart from existing topical agents (sodium sulfacetamide, azelaic acid, metronidazole, and the alpha-adrenergic agonist brimonidine) and systemic medications (tetracyclines, beta-blockers and isotretinoin), new therapies including serine protease inhibitors and mast cell stabilizers may ameliorate rosacea symptoms. However, some of these approaches have not been approved by the Food and Drug Administration. Though the exact pathogenesis of rosacea needs to be clarified, OS and oxidation of lipids are considered as crucial factors to trigger and aggravate the inflammatory processes of rosacea. Increased OS and decreased antioxidants are determined in systemic circulation of rosacea. OS, in addition, is complicated in vascular changes, inflammation, and oxidative tissue damage in rosacea. Therefore, antioxidants may be a potential strategy for treating rosacea. As an essential process in chronic inflammatory dermatoses, angiogenesis also contributes to the development of rosacea. Amal et al. reported that VEGF expression elevated in cutaneous lesions of rosacea and was consistent with vascular histological changes which clinically presented as erythema and telangiectasia. VEGF, indeed, has an important impact on the angiogenesis process, responsible for telangiectasia and increased vascular permeability, leading to cutaneous inflammation and the presence of papules, pustules, and nodules in rosacea. Thus, attenuation of OS and VEGF may be relevant approaches for the therapy of rosacea. However, more research should be carried out to clarify the relationship of OS and angiogenesis and provide a novel therapeutic way for rosacea.

Oxid Med Cell Longev. 2019; 2019: 2304018.
Emerging Roles of Redox-Mediated Angiogenesis and Oxidative Stress in Dermatoses
Dehai Xian, Jing Song, Lingyu Yang,  Xia Xiong,  Rui Lai,  and Jianqiao Zhong

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"Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea."

Int J Mol Sci. 2021 Jan 19;22(2):
Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model.
Lee J, Jung Y, Jeong SW, Jeong GH, Moon GT, Kim M