ANGIOGENESIS PATHWAY, A SPROUTING OF CAPILLARIES FROM THE EXISTING VASCULAR SYSTEM

The angiogenesis pathway is a vital process that enables the formation of new blood vessels from existing ones, a mechanism essential for tissue growth, repair, and development. This pathway plays a crucial role in various physiological processes, including wound healing, organ growth, and embryonic development. However, its regulation is equally critical in diseases, as abnormal angiogenesis can contribute to tumor progression, chronic inflammation, and other vascular disorders.

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Angiogenic signaling pathway and angiogenesis.

KEY MECHANISMS OF ANGIOGENESIS

Angiogenesis is primarily categorized into two types: sprouting angiogenesis and intussusceptive angiogenesis.

Sprouting Angiogenesis: This process involves the migration of endothelial cells (ECs) from existing blood vessels towards angiogenic signals, such as vascular endothelial growth factor (VEGF). Endothelial tip cells lead the sprout, guided by gradients of angiogenic factors, while stalk cells proliferate to elongate the new vessel.
Intussusceptive Angiogenesis: This less understood mechanism occurs when existing blood vessels split to form new ones. It is characterized by the insertion of tissue pillars into the lumen of pre-existing vessels, which can be stimulated by various cytokines, including platelet-derived growth factor (PDGF).

SIGNALING PATHWAYS INVOLVED IN NEW BLOOD VESSELS FORMATION

The angiogenesis pathway is regulated by a complex network of signaling molecules:

VEGF Pathway: VEGF is a key pro-angiogenic factor that promotes endothelial cell proliferation, migration, and survival. It binds to its receptors (VEGFR-1 and VEGFR-2) on endothelial cells, triggering a cascade of intracellular signals that facilitate new blood vessel formation.
PDGF Pathway: PDGF plays a crucial role in vessel maturation and stabilization by recruiting pericytes to newly formed vessels. It also enhances endothelial cell proliferation and migration.
Angiopoietin-Tie Pathway: Angiopoietins (e.g., Ang1 and Ang2) interact with Tie2 receptors on endothelial cells. While Ang1 promotes vessel stabilization, Ang2 acts as an antagonist, promoting vessel destabilization under certain conditions.

MAJOR ANGIOGENIC MARKERS

Several key cellular components contribute to the immune response.

Vascular Endothelial Growth Factor (VEGF): One of the most well-known markers, VEGF promotes the survival, proliferation, and migration of endothelial cells, which line the inside of blood vessels. Its signaling pathway is a primary target in anti-angiogenic therapies for cancer and other diseases.
Fibroblast Growth Factor (FGF): FGFs, particularly FGF2 (basic FGF), stimulate endothelial cell growth and are critical in wound healing, tissue repair, and development.
Angiopoietins (Ang-1, Ang-2): These are involved in stabilizing blood vessels and work in conjunction with the Tie2 receptor on endothelial cells. Ang-1 stabilizes vessels, while Ang-2 can destabilize them, facilitating new vessel sprouting when VEGF is present.
Platelet-Derived Growth Factor (PDGF): PDGF recruits pericytes (cells that wrap around blood vessels) to stabilize newly formed blood vessels, supporting their maturation and structural integrity.
Matrix Metalloproteinases (MMPs): These enzymes break down the extracellular matrix, enabling endothelial cells to migrate and form new vessels.
Endothelial Cell Adhesion Molecules: Examples include PECAM-1 (CD31) and VE-cadherin, which are essential for endothelial cell-cell adhesion and maintaining vascular integrity during angiogenesis.
Integrins (αvβ3, αvβ5): Integrins are adhesion molecules that mediate cell attachment to the extracellular matrix.

ANGIOGENESIS IN CANCER

In normal tissues, angiogenesis is carefully regulated and occurs mainly during wound healing or tissue growth. In cancer, however, tumor cells manipulate this process by secreting angiogenic factors, like Vascular Endothelial Growth Factor (VEGF), to stimulate the formation of blood vessels. These vessels are typically abnormal and leaky, which can facilitate tumor cell invasion into nearby tissues and enable metastasis to distant organs.

CLINICAL RELEVANCE OF ANGIOGENIC MARKERS

In research and clinical settings, angiogenic markers are used to:

Diagnose and monitor diseases associated with abnormal blood vessel growth, such as cancer and diabetic retinopathy.
Develop targeted therapies by identifying pathways or molecules that may be inhibited (e.g., VEGF inhibitors in cancer therapy).
Assess treatment efficacy by measuring changes in marker levels, indicating either inhibition or promotion of angiogenesis.

Anti-angiogenic therapies aim to block these pathways, essentially "starving" the tumor by cutting off its blood supply. Some of the most common anti-angiogenic agents include VEGF inhibitors, Tyrosine kinase inhibitors and Anti-angiogenic antibodies.

(1) Ma Q, et al. Role of melatonin in controlling angiogenesis under physiological and pathological conditions. Angiogenesis. (2020);23(2):91-104.

(2) Huang YJ, Nan GX. Oxidative stress-induced angiogenesis. J Clin Neurosci. (2019);63:13-16.

(3) Mukherjee A, et al. Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer. Int J Mol Sci. (2020);21(2):455.

(4) Braile M, et al. VEGF-A in Cardiomyocytes and Heart Diseases. Int J Mol Sci. (2020);21(15):5294.

(5) Lee HJ, et al. Angiogenesis in Chronic Inflammatory Skin Disorders. Int J Mol Sci. 2021 Nov 7;22(21):12035.

(6) Loizzi V, et al. Biological Pathways Involved in Tumor Angiogenesis and Bevacizumab Based Anti-Angiogenic Therapy with Special References to Ovarian Cancer. Int J Mol Sci. (2017)14;18(9):1967

ANGIOGENESIS SIGNALING PATHWAY BIOMARKER LIST

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to get started on your project.

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Signaling Pathways	Product ref	Informations
Angiogenesis	AN1H1	List infos
Angiogenesis	AN2H1	List infos

Species : Mus musculus (mouse)

Signaling Pathways	Product ref	Informations
Angiogenesis	AN1M1	List infos
Angiogenesis	AN2M1	List infos

Species : Rattus norvegicus (rat)

Signaling Pathways	Product ref	Informations
Angiogenesis	*******	List In progress...

Species : Sus Scrofa (Pig)

Signaling Pathways	Product ref	Informations
Angiogenesis	*******	List In progress...

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