Address correspondence to: Anthony P. Hall, AstraZeneca R&D Alderley Park, Safety Assessment UK, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, England; e-mail: Peter. A. Hall@ astrazeneca. com Abbreviations: αSMA, alpha smooth muscle actin; Ang, angiopoietin; Cx, connexin; Edg-1, endothelial differentiation gene; Enos, endothelial nitric oxide synthase; flk-1/VEGFR-2+, foetal liver kinase-1/vascular endothelial growth factor receptor-2; GFP green fluorescent protein; HB-EGF heparin binding-epidermal growth factor-like growth factor; MMP-2 matrix metalloproteinase-2; PDGF-B platelet derived growth factor-B; PDGFRβ platelet derived growth factor receptor β; Sca-1+ stem cell antigen; S1P, sphingosine-1-phosphate; TGF-β1, transforming growth factor β1; Tie-1, endothelial tyrosine kinases; VSMC, vascular smooth muscle cell; VEGF, vascular endothelial growth factor. effects (Bergers et al., 2003; Erber et al., 2004), and may welcome in a new era of molecularly targeted drugs.

MORPHOLOGY AND DISTRIBUTION Classically, mature pericytes form intimate, umbrella-like contacts with the endothelial cells in capillaries, pre-capillary arterioles, collecting venules and postcapillary venules. Endothelial cells and pericytes both synthesise and share a common basement membrane (Mandarino et al., 1993). Pericytes communicate with endothelial cells directly through peg-and-socket junctions that extend through a discontinuous basement membrane (Cuevas et al., 1984). These junctions consist of membrane evaginations that are rich in tight and gap junctions. Pericyte-endothelial adhesion, recognition and signalling are also maintained by N-cadherin adhesion junctions (Gerhardt et al., 2000) and fibronectin-rich dense plaques (Courtoy and Boyles, 1983). It is now apparent that these umbrella-like processes extend to more than one capillary (Ando et al., 1999) and are more extensive on venous capillaries and post-capillary venules (reviewed by Hirschii and D’Amore, 1996). Pericyte coverage per se is also more extensive on post-capillary venules than capillaries, with overall pericyte coverage (in the rat) varying between 11% in cardiac muscle to 41% in the retina (Sims, 1991). Pericytes are also more numerous in the distal regions of limbs (Sims et al., 1994), predominate over endothelial junctions in the ocular choroid, lung and skin (Sims and westfall, 1983) and are polarised over endothelial surfaces not involved in gas exchange (reviewed in Gerhardt and Betsholtz, 2003). The bias of pericytes towards the distal venular compartment strongly hints at their role in vivo, which is to support the microcirculation against hydrostatic pressure.