Pathologic vascular findings in IPF consist of changes in the arteries, arterioles, and venules, and destruction of the capillary bed, which are traditionally attributed to hypoxia and fibrosis, respectively. Advential thickening around the pulmonary vessels occurs due to an increase of fibroblasts, myofibroblasts, and extracellular matrix deposition. Smooth-muscle cell hypertrophy and proliferation and collagen and elastin accumulation occur in the media of the small muscular pulmonary arteries, and distal pulmonary arterioles become muscularized. These changes are consistent with those seen in other hypoxia-related lung diseases. In addition, there may be extensive intimal hyperplasia, fibrosis, and reduplication of the inner elastic lamina in the small muscular pulmonary arteries in IPF; such changes are not usually observed in animal models or patients with hypoxia-related lung disease alone.16–21 These findings are present in densely fibrotic lobules (Fig 2
, top left, A, and top right, B) as well as in less fibrotic areas (center left, C, through bottom right, F).,21–In situ thrombosis has also been observed in small muscular pulmonary arteries.22 More recently, investigators21 have documented intimal proliferation and fibrosis in the pulmonary venules as well.