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Angiogenesis

Refers to a process involving tight regulation of multiple signaling pathways by which new blood vessels are formed from pre-existing vessels.

Consists of highly complex biochemical and cellular processes with sequential receptor activation by several growth factors, including acidic fibroblast growth factor (FGF), transforming growth factor (TGF)=alpha, TGF-beta, hepatocyte growth factor, tumor necrosis factor-a[pha, angiogenin, IL-8, angiopoietins.

A homeostatic process which occurs mainly during embryongenesis but also occurs in adults during the ovarian cycle and in normal physiological wound healing repair.

Mesodermal cells differentiate to angioblasts which are committed to arterial or venous lineage.

Angioblasts aggregate, proliferate and differentiate into endothelial tubes of arterial and venous vascular networks joining to become a cardiovascular loop in the process of vasculogenesis.

Mediated by growth factors that induce endothelial cells to proliferate, migrate, assemble and recruit perivascular cells such as smooth muscle cells and remodels extracellular matrix.

Development of new blood vessels from a preexisting vascular bed.

Physiologic angiogenesis is required for human growth, development, maintenance, and repair.

Pathologic angiogenesis in response to hypoxemia or inflammation enables tumor growth and causes tissue destruction.

Malignancies often exploit angiogenic processes to stimulate tumor growth and disease progression.

When deregulated can contribute to the development of multiple processes including: cancer, cardiovascular disease, diabetes and arthritis.

Process of new blood vessel formation from preexisting ones involved in inflammation and tumor growth.

The process is usually suppressed but can be transiently activated during wound healing and menstruation.

Uncontrolled angiogenesis occurs in rheumatoid arthritis, diabetes and malignancy.

Fundamental to tumor growth.

VEGF is the dominant proangiogenic vascular growth factor controlling blood vessel formation.

VEGF and its receptor VEGF receptor 2 on the most prominent regulate his of angiogenesis.

VEGF is a critical rate limiting molecule in angiogenesis.

VEGF signaling stimulates cellular pathways that form new tumor blood vessels, promote rapid tumor growth, and facilitate metastases.

Angiogenesis during embryological growth requires VEGF, and without it death occurs.

Simple diffusion of nutrients and oxygen up to a size of 1-2 mm beyond which further growth requires the establishment of a vascular supply.

Implicated in progression from premalignant tumor to carcinoma, invasion of tumor into the systemic circulation and growth of latent microscopic disease into frank metastatic lesions.

Plays of role in tumor metastases by providing access to systemic lymphatic and circulatory channels.

Stimulated by factors released from tumor cells, inflammatory cells or the extracellular matrix.

Factors that stimulate neovascularization include basic fibroblast growth factor, transforming growth factor ß, vascular endothelial growth factor (VEGF), platelet derived endothelial growth factor (PDGF) E-cathedrin and angiogenin.

Also occurs as a response to injury with interaction of hemostatic and inflammatory systems and is regulated by cytokines and growth factors that act to regulate cellular proliferation and tissue repair.

In the absence of angiogenesis tumors remain mainly dormant with a maximum diameter of 100-200 µm limited by diffusion of oxygen, glucose and waste products.

Local release of VEGF and other factors from malignant and inflammatory cells promotes blood vessel permeability with leakage of plasma proteins forming a scaffold for endothelial cells to migrate.

Through this process tumor cells acquire capabilities to grow, survive, and metastasize.

Proangiogenic factors include transcription factors, oncogenes such as src, raf, ras, mutated suppressor genes p53, von Hippel-Lindau and growth factors EGF.

Synergy exists when antiangiogenic agents are added to chemotherapy and radiation therapy.

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