The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.
The pathobiology of pulmonary hypertension. Endothelium.
R M Tuder; C D Cool; M Yeager; L Taraseviciene-Stewart; T M Bull; N F Voelkel (Profiled Author: Rubin Tuder)
Departments of Pathology, and Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA. Rtuder@JHMI.EDU
Clinics in chest medicine 2001;22(3):405-18.
Dysfunctional endothelial cells have a central and critical role in the initiation and progression of severe pulmonary hypertension. The elucidation of the mechanisms involved in the control of endothelial cell proliferation and cell death in the pulmonary vasculature, therefore, is fundamentally important in the pathogenesis of severe pulmonary hypertension and of great interest for a better understanding of endothelial cell biology. Because the intravascular growth of endothelial cells resulting in tumorlets is unique to severe pulmonary hypertension, this phenomenon can teach researchers about the factors involved in the formation and maintenance of the normal endothelial cell monolayer. Clearly, in severe pulmonary hypertension, the "law of the endothelial cell monolayer" has been broken. The ultimate level of such a control is at the altered gene expression pattern that is conducive to endothelial cell growth and disruption of pulmonary blood flow. Secondary pulmonary hypertension certainly also is associated with proliferated pulmonary endothelial cells and plexiform lesions that are histologically indistinguishable from those in PPH. What is then the difference in the mechanisms of endothelial cell proliferation between primary and secondary pulmonary hypertension? The authors believe that PPH is a disease caused by somatic mutations in key angiogenesis- or apoptosis-related genes such as the TGF-beta receptor-2 and Bax. The loss of these important cell growth control mechanisms allows for the clonal expansion of endothelial cells from a single cell that has acquired a selective growth advantage. On the other hand, the proliferated endothelial cells in secondary pulmonary hypertension are polyclonal. It follows from this finding that local (vascular) factor(s) (such as increased shear stress), rather than mutations, play a major role in triggering endothelial cell proliferation. In PPH and secondary pulmonary hypertension, the researcher can postulate that the pulmonary vascular bed contains progenitor-like cells with the capacity of dysregulated growth. The main difference in the pathogenesis of primary and secondary pulmonary endothelial cell proliferation therefore may be the initial mechanism involved in the recruitment of an endothelial progenitor-like cell. In PPH, anorexigen-associated, and familial PPH, the proliferation of endothelial cells occurs from a mutated single cell, whereas in secondary pulmonary hypertension, several progenitor-like cells would be activated to grow. The abnormal endothelial cells in both forms of severe pulmonary hypertension expand because of the expression of angiogenesis-related molecules such as VEGF, VEGFR-2, HIF-1 alpha, and HIF-beta. Also important for the expansion of these cells is the down-regulation of expression of apoptosis-related mediators such as TGF-beta receptor-2 or Bax. The success of any therapy for severe pulmonary hypertension requires that the underlying process of endothelial cell proliferation could be controlled or reversed.
This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.
C D Cool; J S Stewart; P Werahera; G J Miller; R L Williams; N F Voelkel; R M Tuder
Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers. Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth.The American journal of pathology 1999;155(2):411-9.
Norbert F Voelkel; Carlyne Cool; Laima Taraceviene-Stewart; Mark W Geraci; Michael Yeager; Todd Bull; Michael Kasper; Rubin M TuderCritical care medicine 2002;30(5 Suppl):S251-6.
R M Tuder; M Chacon; L Alger; J Wang; L Taraseviciene-Stewart; Y Kasahara; C D Cool; A E Bishop; M Geraci; G L Semenza; et al.The Journal of pathology 2001;195(3):367-74.
Appears in this Publication
Author of this Publication