Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 170, Issue 12, Pages 1340-1348Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200311-1602OC
Keywords
enclothelial cells; pulmonary hypertension; Smad; smooth muscle cells; transforming growth factor-beta
Categories
Funding
- NHLBI NIH HHS [P01-HL66254] Funding Source: Medline
Ask authors/readers for more resources
Mutations in transforming growth factor-beta family receptor-II, bone morphogenetic protein receptor-2, and activin-like kinase-1 have been associated with pulmonary hypertension. In the present study, we determined that pulmonary arteries in normal lungs and in lungs of patients with emphysema and idiopathic pulmonary arterial hypertension comparably expressed transforming growth factor-beta receptors I and II, Smad(1, 5, 8), Smad2, Smad3, Smad4, phosphorylated Smad (1, 5, 8), and phosphorylated Smad2 (the latter two both indicative of active in vivo signaling) in endothelial cells, as assessed by immunohistochemistry and quantitative morphometry. Medial or intimal smooth muscle cells had weak or absent expression of these molecules. In clear contrast to endothelial cell expression in pulmonary arteries and in endothelial cells lining incipient vessels within plexiform lesions of hypertensive lungs, endothelial cells present in the core of the lesions lacked expression of all examined members of the signaling molecules. These findings were made irrespective of the mutation status of bone morphogenetic protein receptor-2 in hypertensive patients. Our findings suggest that pulmonary artery endothelial cells in both normal and severely hypertensive lungs have active transforming growth factor-beta family signaling, and that loss of signaling might contribute to the abnormal growth of endothelial cells in plexiform lesions in idiopathic pulmonary arterial hypertension.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available