ANGIOGENESIS AND LYMPHANGIOGENESIS IN CHRONIC INFLAMMATION

D. McdonaldUniversity of California, San Francisco, United StatesBlood vessels and lymphatic vessels are important in normal organ physiology and play key roles in the pathophysiology disease. By undergoing adaptive growth and remodeling, blood vessels undergo changes that result in their expansion and remodeling that enables plasma extravasation and leukocyte influx into inflamed tissues. Lymphatic vessels provide key routes for drainage of interstitial fluid from tissues. Edema, a cardinal sign of inflammation and clinically significant feature of inflammatory disease, results when the amount of leakage from inflamed blood vessels exceeds the capacity for drainage. Lymphatic vessels adjust to the increased fluid clearance and leukocyte traffic in inflammation. Inhibition of VEGFR-3 signaling completely prevents the expansion of tissue lymphatics but not blood vessels, but the lack of lymphatic growth exaggerates tissue edema. Blood vessels and lymphatics in the adult are strikingly different from those of late-stage embryos. Before birth, blood vessels in some organs lack the normal hierarchy and organ specialization of the adult but instead constitute a primitive plexus similar to that of the yolk sac. The primitive plexus undergoes rapid and extensive remodeling at birth. In the early neonatal period, parts of the plexus regress. Capillaries then rapidly regrow, and with the maturation of arteriolar and venular segments, form the characteristic adult vasculature that responds in inflammation. Lymphatic vessels also undergo rapid changes around birth, when lymphatic endothelial cells develop button-like intercellular junctions specialized for efficient fluid uptake. Among the mechanisms that underlie the onset of rapid vascular remodeling at birth, changes in tissue oxygen tension and mechanical forces associated with breathing are likely to be involved, along with growth factors that promote the growth and maturation of blood vessels and lymphatics by sprouting angiogenesis and lymphangiogenesis and remodeling of existing vessels. The dynamic nature of blood vessels and lymphatics during perinatal development foretells the extraordinary vascular plasticity found in sustained inflammation. Because of this plasticity, blood vessels and lymphatics are sensitive indicators of environmental cues and tissue requirements that change during normal development, at birth, and in disease. The plasticity requires a mechanism for rapid transformation of blood vessels and lymphatics by remodeling of existing vessels integrated with expansion by sprouting angiogenesis and lymphangiogenesis. Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 9Session: Angiogenesis and lymphangiogenesis as potential therapeutic targets in rheumatic diseases (Speaker Presentations )