In VivoPericyte–Endothelial Cell Interaction during Angiogenesis in Adult Cardiac and Skeletal Muscle

Abstract

Pericytes (PC) exert an inhibitory effect on endothelial cell (EC) proliferationin vitroand withdrawal of PC occurs prior to EC proliferation during pathological capillary growthin vivo.Using stereological analyses of PC and capillary EC fine structure, we have studied their relationship during the early stages of physiological angiogenesis using twoin vivomodels. In rat skeletal muscle where capillary growth was induced by indirect electrical stimulation, there was a reduction in the relative area of contact between pericytes and the capillary abluminal surface (22% vs 30% for normal controls;P< 0.05) and pericyte surface:volume ratio (12.5 vs 14.9 μm⁻¹for normal controls;P< 0.05) after 3 days of stimulation, at a time prior to the appearance of new capillaries. Further withdrawal of pericyte processes was evident at the point where an actual increase in capillary numbers was observed (7 days stimulation; PC surface:volume ratio = 10.4 μm⁻¹), although the degree of PC–EC interdigitation increased. Similar changes, but to a lesser extent, were observed in both left ventricular myocardium and papillary muscles of pigs following 4–5 weeks chronic heart rate reduction. Although PC coverage of capillaries in the heart was found to be less than that in skeletal muscle, the relative contact area between PC and capillaries also showed a reduction in paced vs sham-operated control heart (papillary: 15% vs 20%; ventricle: 12% vs 16%;P< 0.05). Interdigitation of PC and EC was absent in cardiac muscle. These data suggest that retraction of PC may play a permissive role in controlling angiogenesisin vivoin normal adult tissue.