Published ahead of print on February 10, 2006, doi:10.1165/rcmb.2005-0387OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0387OC Tissue-Specific Renin–Angiotensin System in Pulmonary Lymphangioleiomyomatosis Pulmonary-Critical Care Medicine Branch and Pathology Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Biophysics Department, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and Laboratoire d'Anatomie Pathologique, Hôpital Européen Georges Pompidou, Paris, France Correspondence and requests for reprints should be addressed to Joel Moss, M.D, Ph.D., Chief, Pulmonary–Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10/Room 6D05 MSC-1590, Bethesda, MD 20892-1590. E-Mail: mossj{at}nhlbi.nih.gov
Lymphangioleiomyomatosis (LAM), a multisystem disease found in middle-aged women, is characterized by cystic lung destruction and abdominal tumors (e.g., angiomyolipomas, lymphangioleimyomas), resulting from proliferation of abnormal-appearing, smooth muscle–like cells (LAM cells). The LAM cells, in combination with other cells, form nodular structures within the lung interstitium and in the walls of the cysts. LAM cells contain mutations in the tuberous sclerosis complex TSC1 and/or TSC2 genes, which lead to dysregulation of the mammalian target of rapamycin, affecting cell growth and proliferation. Proliferation and migration of vascular smooth muscle cells and production of angiogenic factors are regulated, in part, by angiotensin II. To determine whether a LAM-specific renin–angiotensin system might play a role in the pathogenesis of LAM, we investigated the expression of genes and gene products of this system in LAM nodules. mRNA for angiotensinogen was present in RNA isolated by laser-captured microdissection from LAM nodules. Angiotensin I–converting enzyme and chymase-producing mast cells were present within the LAM nodules. We detected renin in LAM cells, as determined by the presence of mRNA and immunohistochemistry. Angiotensin II type 1 and type II receptors were identified in LAM cells by immunohistochemistry and immunoblotting of microdissected LAM nodules. Angiotensin II is localized in cells containing
Key Words: angiotensin II • lymphangioleiomyomatosis • mammalian target of rapamycin • smooth muscle cells • tuberous sclerosis complex This article has been cited by other articles:
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–smooth muscle actin (LAM cells). A LAM-specific renin–angiotensin system appears to function within the LAM nodule as an autocrine system that could promote LAM cell proliferation and migration, and could represent a pharmacologic target. 
