The molecular basis of physiological angiogenesis
When an organism or tissue grows beyond a size where passive
diffusion for the exchange of oxygen, nutrients and metabolic waste
products becomes insufficient, the need for the development of a vascular
system emerges. Angiogenesis is the process by which the organism
establishes new blood vessels from pre-existing ones (Fig. 1). Recent
studies have highlighted the fundamental aspects of vessel formation, including
vasculogenic assembly, vessel sprouting, lumen formation and
vascular remodeling [3,4].
Sprouting of endothelial cells (EC) is the first in a sequence of events
during angiogenesis [5]. In a resting vessel, both endothelial and mural
cells form a basement membrane around the vessel tube, preventing
resident EC to migrate.When newblood vessels are needed in a growing
tissue, local production of angiogenic growth factors is enhanced, which
trigger the EC to degrade the basement membrane extracellular matrix,
a process mediated by matrix metalloproteinases (MMPs). The action of
these MMPs further fortifies the angiogenic response by releasing
proangiogenic factors that were stored within the matrix. Attracted by
the angiogenic signals, some EC become motile and express filopodia.