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Regular Articles |
From the Pulmonary Hypertension Center*
and the
Departments of Pathology
and Respiratory and Critical
Care Medicine,
University of Colorado Health Sciences
Center, Denver, Colorado
The plexiform lesions of severe pulmonary hypertension (PH) are complex vascular structures composed primarily of endothelial cells. In this study, we use immunohistochemical markers to identify the various cell layers of pulmonary vessels and to identify different endothelial cell phenotypes in pulmonary arteries affected by severe PH. Our computerized three-dimensional reconstructions of nine vessels in five patients with severe PH demonstrate that plexiform (n = 14) and concentric-obliterative (n = 6) lesions occur distal to branch points of small pulmonary arteries. And, whereas plexiform lesions occur as solitary lesions, concentric-obliterative lesions appear to be only associated with, and proximal to, plexiform structures. The endothelial cells of plexiform lesions express intensely and uniformly the vascular endothelial growth factor (VEGF) receptor KDR and segregate phenotypically into cyclin-kinase inhibitor p27/kip1-negative cells in the central core of the plexiform lesion and p27/kip1-positive cells in peripheral areas adjacent to incipient blood vessel formation. Using immunohistochemistry and three-dimensional reconstruction techniques, we show that plexiform lesions are dynamic vascular structures characterized by at least two endothelial cell phenotypes. Plexiform arteriopathy is not merely an end stage or postthrombotic change—it may represent one stage in an ongoing, angiogenic endothelial cell growth process.
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M.M. Hoeper Pulmonary hypertension in collagen vascular disease Eur. Respir. J., March 1, 2002; 19(3): 571 - 576. [Abstract] [Full Text] [PDF]
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P. M. Becker, A. D. Verin, M. A. Booth, F. Liu, A. Birukova, and J. G. N. Garcia Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1500 - L1511. [Abstract] [Full Text] [PDF]
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 T. Stevens, R. Rosenberg, W. Aird, T. Quertermous, F. L. Johnson, J. G. N. Garcia, R. P. Hebbel, R. M. Tuder, and S. Garfinkel NHLBI workshop report: endothelial cell phenotypes in heart, lung, and blood diseases Am J Physiol Cell Physiol, November 1, 2001; 281(5): C1422 - C1433. [Abstract] [Full Text] [PDF]
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N. W. Morrell, X. Yang, P. D. Upton, K. B. Jourdan, N. Morgan, K. K. Sheares, and R. C. Trembath Altered Growth Responses of Pulmonary Artery Smooth Muscle Cells From Patients With Primary Pulmonary Hypertension to Transforming Growth Factor-{beta}1 and Bone Morphogenetic Proteins Circulation, August 14, 2001; 104(7): 790 - 795. [Abstract] [Full Text] [PDF]
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 R. C. Trembath, J. R. Thomson, R. D. Machado, N. V. Morgan, C. Atkinson, I. Winship, G. Simonneau, N. Galie, J. E. Loyd, M. Humbert, et al. Clinical and Molecular Genetic Features of Pulmonary Hypertension in Patients with Hereditary Hemorrhagic Telangiectasia N. Engl. J. Med., August 2, 2001; 345(5): 325 - 334. [Abstract] [Full Text] [PDF]
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R. M. Tuder and N. F. Voelkel Plexiform Lesion in Severe Pulmonary Hypertension: Association with Glomeruloid Lesion Am. J. Pathol., July 1, 2001; 159(1): 382 - 383. [Full Text] [PDF]
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M. W. Geraci, M. Moore, T. Gesell, M. E. Yeager, L. Alger, H. Golpon, B. Gao, J. E. Loyd, R. M. Tuder, and N. F. Voelkel Gene Expression Patterns in the Lungs of Patients With Primary Pulmonary Hypertension : A Gene Microarray Analysis Circ. Res., March 30, 2001; 88(6): 555 - 562. [Abstract] [Full Text] [PDF]
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L. TARASEVICIENE-STEWART, Y. KASAHARA, L. ALGER, P. HIRTH, G. MC MAHON, J. WALTENBERGER, N. F. VOELKEL, and R. M. TUDER Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension FASEB J, February 1, 2001; 15(2): 427 - 438. [Abstract] [Full Text] [PDF]
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T. NISHIMURA, J. L. FAUL, G. J. BERRY, I. VEVE, R. G. PEARL, and P. N. KAO 40-O-(2-Hydroxyethyl)-rapamycin Attenuates Pulmonary Arterial Hypertension and Neointimal Formation in Rats Am. J. Respir. Crit. Care Med., February 1, 2001; 163(2): 498 - 502. [Abstract] [Full Text]
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S. Archer and S. Rich Primary Pulmonary Hypertension : A Vascular Biology and Translational Research "Work in Progress" Circulation, November 28, 2000; 102(22): 2781 - 2791. [Abstract] [Full Text] [PDF]
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C. Atkinson, S. Stewart, P. D. Upton, R. Machado, J. R. Thomson, R. C. Trembath, and N. W. Morrell Primary Pulmonary Hypertension Is Associated With Reduced Pulmonary Vascular Expression of Type II Bone Morphogenetic Protein Receptor Circulation, April 9, 2002; 105(14): 1672 - 1678. [Abstract] [Full Text] [PDF]
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