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Gene Expression Profiles in Pulmonary Hypertension* FREE TO VIEW

Mark W. Geraci, MD; Yasushi Hoshikawa, MD; Michael Yeager; Heiko Golpon, MD; Tracy Gesell; Rubin M. Tuder, MD; Norbert F. Voelkel, MD
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*From the University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Norbert Voelkel, MD, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, 4200 E 9th Ave, Box C272, Denver, CO 80262; e-mail: norbert.voelkel@uchsc.edu

Chest. 2002;121(3_suppl):104S-105S. doi:10.1378/chest.121.3_suppl.104S
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Chronic pulmonary hypertension is associated with structural alterations of the large and small pulmonary arteries in which smooth muscle and endothelial cells interact in a process of vascular “remodeling.” Because the vascular lesions are ubiquitously distributed in the lung, random lung tissue samples can be used for microarray gene chip expression analysis. We found a signature expression profile in the lungs from patients with sporadic primary pulmonary hypertension (PPH), when compared with the gene expression profile found in healthy lungs and, importantly, when compared with the gene expression profile found in the lungs from patients with familial PPH. Chronic hypoxia-induced lung vascular remodeling, which histologically is characterized by pulmonary arterial smooth muscle hypertrophy, is modulated by the administration of prostacyclin. Mice that overexpress the critical enzyme prostacyclin synthase in their lungs and mice with a knockout of the prostacyclin receptor show altered expression of a number of genes in their lungs when compares with wild-type animals and also show that there are genes that depend on signaling through the prostacyclin membrane receptor for their expression. In the aggregate, our expression studies show that different molecular mechanisms are involved in the hypertensive lung vascular remodeling in humans (PPH) and in mice (chronic hypoxia-induced pulmonary hypertension).

Abbreviation: PPH = primary pulmonary hypertension




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