Angiogenesis in Pulmonary Fibrosis Chandru Hanumegowda, PhD, Laszlo Farkas, MD, Martin Kolb, MD, PhD  CHEST  Volume 142, Issue 1, Pages 200-207 (July 2012) DOI: 10.1378/chest.11-1962 Copyright © 2012 The American College of Chest Physicians Terms and Conditions

Figure 1 The concept of angiogenesis in pulmonary fibrosis. There is reduced small vessel density in fibroblastic foci (FF) and dense scar tissue in some areas of the fibrotic lung, whereas the sections between normal and fibrotic tissue contain more microvascular structures. Dilated larger vessels and bronchopulmonary anastomoses are found in areas with honeycombing and bronchiectasis. The local microenvironment has a major influence not only on fibrogenesis but also on vessel homeostasis and angiogenesis. For example, angiogenic factors such as VEGF and FGF, which also have profibrotic properties, are decreased in FF but increased in the surrounding tissue, similar to angiogenic ELR+ CXC chemokines. In contrast, the expression of angiostatic elements (eg, PEDF and endostatin) is high in FF and low in the surroundings. The density of microvessels is overall reduced in fibrotic lungs, thus contributing to the development of pulmonary hypertension. AEC = alveolar epithelial cell; ELR = three-amino-acid sequence (glutamic acid-leucine-arginine); FGF = fibroblast growth factor; PEDF = pigment epithelium-derived factor; VEGF = vascular endothelial growth factor. CHEST 2012 142, 200-207DOI: (10.1378/chest.11-1962) Copyright © 2012 The American College of Chest Physicians Terms and Conditions

Figure 2 Fibrosis, angiogenesis/vessel density and growth factors are closely interrelated inidiopathic pulmonary fibrosis (IPF). Two major scenarios are plausible: (1) fibrosis causes impaired angiogenesis through growth factor abnormalities and thereby vessel loss in some areas of the lung but increased vessel density in others, possibly as a mechanism to control fibrogenic signals, with the net effect being reduced vascular surface area and development of pulmonary hypertension. (2) Impaired angiogenic signals and vessel density cause abnormal tissue repair and thereby promote fibrosis progression. It is yet unclear if the abnormal vasculature found in IPF lungs is cause or consequence of the disease, or, in keeping with the illustration, which one of the wheels turns first. ++ = increase of fibrosis and growth factor activity; −− = decrease in vessel density. CHEST 2012 142, 200-207DOI: (10.1378/chest.11-1962) Copyright © 2012 The American College of Chest Physicians Terms and Conditions