HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/L548    most recent 00428.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Masri, F. A. Articles by Erzurum, S. C. Search for Related Content PubMed PubMed Citation Articles by Masri, F. A. Articles by Erzurum, S. C.

EDITORIAL FOCUS

Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension

¹Departments of Pathobiology, ³Imaging Facility, ⁴Cole Eye Institute, and ⁵Pulmonary, Allergy and Critical Care Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland; and ²Cleveland State University, Cleveland, Ohio

Submitted 30 October 2006 ; accepted in final form 23 May 2007

Idiopathic pulmonary arterial hypertension (IPAH) is characterized by plexiform vascular lesions, which are hypothesized to arise from deregulated growth of pulmonary artery endothelial cells (PAEC). Here, functional and molecular differences among PAEC derived from IPAH and control human lungs were evaluated. Compared with control cells, IPAH PAEC had greater cell numbers in response to growth factors in culture due to increased proliferation as determined by bromodeoxyuridine incorporation and Ki67 nuclear antigen expression and decreased apoptosis as determined by caspase-3 activation and TdT-mediated dUTP nick end labeling assay. IPAH cells had greater migration than control cells but less organized tube formation in in vitro angiogenesis assay. Persistent activation of signal transducer and activator of transcription 3 (STAT3), a regulator of cell survival and angiogenesis, and increased expression of its downstream prosurvival target, Mcl-1, were identified in IPAH PAEC. A Janus kinase (JAK) selective inhibitor reduced STAT3 activation and blocked proliferation of IPAH cells. Phosphorylated STAT3 was detected in endothelial cells of IPAH lesions in vivo, suggesting that STAT3 activation plays a role in the proliferative pulmonary vascular lesions in IPAH lungs.

STAT3; apoptosis

This article has been cited by other articles:

				T. Stevens, S. Phan, M. G. Frid, D. Alvarez, E. Herzog, and K. R. Stenmark Lung Vascular Cell Heterogeneity: Endothelium, Smooth Muscle, and Fibroblasts Proceedings of the ATS, September 15, 2008; 5(7): 783 - 791. [Abstract] [Full Text] [PDF]

				P. R. Rai, C. D. Cool, J. A. C. King, T. Stevens, N. Burns, R. A. Winn, M. Kasper, and N. F. Voelkel The Cancer Paradigm of Severe Pulmonary Arterial Hypertension Am. J. Respir. Crit. Care Med., September 15, 2008; 178(6): 558 - 564. [Abstract] [Full Text] [PDF]

				J. Huang, P. M. Kaminski, J. G. Edwards, A. Yeh, M. S. Wolin, W. H. Frishman, M. H. Gewitz, and R. Mathew Pyrrolidine dithiocarbamate restores endothelial cell membrane integrity and attenuates monocrotaline-induced pulmonary artery hypertension Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1250 - L1259. [Abstract] [Full Text] [PDF]

				S. Mukhopadhyay, M. Shah, F. Xu, K. Patel, R. M. Tuder, and P. B. Sehgal Cytoplasmic provenance of STAT3 and PY-STAT3 in the endolysosomal compartments in pulmonary arterial endothelial and smooth muscle cells: implications in pulmonary arterial hypertension Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L449 - L468. [Abstract] [Full Text] [PDF]