Proliferation and migration of vascular endothelial cells (ECs) are critical
steps in angiogenesis and are strictly controlled by a number extracellular stimula.
Proangiogenic peptides binding to tyrosine kinase receptors (i.e. VEGFs and FGFs) are
released by several cell types, including ECs and tumor cells. Proangiogenic
intracellular signalling cascades involve many messengers working in a sort of network.
In particular, in this chapter, we describe the properties and functions of the intracellular
calcium signals (Cai), a universal, evolutionary conserved and highly versatile pathway
involved in the regulation of EC proliferation and migration.
Angiogenic factors generate Cai rises via two mechanisms: entry from extracellular
medium, through the opening of calcium-permeable channels in the plasmamembrane,
or release from intracellular Ca2+ stores. Calcium entry, the main topic of this chapter,
can be dependent on previously InsP3-activated emptying of calcium stores (storeoperated
Ca2+ entry - SOCE), or independent on it (non store-operated Ca2+ entry -
NSOCE). The intracellular pathways underlying endothelial Ca2+ entry involve, among
the other pathways, arachidonic acid (AA) and nitric oxide (NO) metabolism. Even if
some Ca2+ entry blockers are under clinical trial with encouraging results, a better
knowledge about the molecular nature of proangiogenic Ca2+ channels and their
intracellular regulation in healthy and pathological processes could lead to new and
more powerful strategies in the therapeutical approaches aimed to interfere with altered
tissue vascularization. Here, we discuss the state of the art in the field of calcium
signaling and angiogenesis, the related recent literature and patents.
Keywords: Angiogenesis, angiogenic factors, antiangiogenic factors, arachidonic
acid, calcium channel blockers, calcium channels, calcium-dependent
transcription factors, calcium entry, calcium signaling, eicosanoids, endothelial
cells, neovascularization, nitric oxide, NOS, PLA2, signal transduction, TRP,
tumor-derived endothelial cells, tyrosine kinase receptors, VEGF.
