Physiological stimuli during wound healing and during the reproductive cycle in women lead to controlled angiogenesis. However, pathologic conditions such as tumour growth, rheumatoid arthritis, and diabetic retinopathy are also characterized by abundant angiogenesis. Angiogenesis is rapidly initiated in response to hypoxic or ischaemic conditions. In tumour growth, this active vascular remodelling is reflected by enhanced tumour endothelial cell
Figure 9.1. In tumours that have undergone the angiogenic switch, the expression of a variety of growth factors and other soluble molecules, and the changes in the extracellular matrix (ECM), among others, lead to angiogenesis, the formation of new blood vessels from pre-existing ones. In this process, endothelial cells (EC) covering the blood vessel wall become activated, migrate into the tissue, proliferate and eventually differentiate into mature blood vessels. These vessels serve as a supply of nutrients for the ongoing demands of the growing tumour cells.
proliferation to up to 20-2000 times faster than in healthy adult endothelium . In all types of angiogenesis, either under physiological or pathologicaal conditions, endothelial cell activation is followed by matrix degradation, cellular migration, proliferation, and ultimately neovasculature maturation (Figure 9.1).
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