RELATIONSHIP OF THE EXTRACELLULAR-MATRIX TO CORONARY NEOVASCULARIZATION DURING DEVELOPMENT

The main goal of this study was to determine the temporal and spatial relationship of several components of the extracellular matrix (ECM) t o coronary vascularization during prenatal and early postnatal develop ment. Rat microvessels were visualized by immunolabeling for platelet endothelial cell adhesion molecule (PECAM-1), and by exposure to the l ectin from Griffonia simplicifolia I. Coronary vasculogenesis, which f irst occurs in gestation day 13 (E13) hearts, was preceded by the depo sition of fibronectin. The onset of laminin immunoreactivity in baseme nt membranes coincided with tube formation and was followed by the app earance of collagen IV. Discontinuous collagen TV staining of basement membranes typified early tube formation but progressed to completely encircle capillaries. Sparse staining of collagen I and III was observ ed in prenatal hearts, but increased after birth. Staining for both mo lecules was limited mainly to the adventitia of vessels larger than ca pillaries, and as a component of septa and the epicardium. To determin e the effects of loading conditions on key ECM molecules relating to n eovascularization, avascular E12 rat hearts were grafted to the anteri or eye chamber of adult hosts. In these hearts, which are hemodynamica lly unloaded, the appearance and distribution of ECM components were s imilar to hearts developing in utero. It was concluded that during hea rt development: (2) fibronectin may provide a primary scaffolding for the migration of primordial endothelial cells/angioblasts; (2) tube fo rmation coincides with Iamin deposition and is closely followed by the appearance of collagen TV; (3) collagens I and III are not related to tube formation in the prenatal heart; and (4) the relationship of the ECM to vessel formation is not notably altered in the absence of a ve ntricular load. Furthermore the early onset of PECAM-1 immunoreactivit y suggests that it is a useful endothelial marker and may play a role in tube formation. (C) 1996 Academic Press Limited