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Endothelial Apoptosis and Repair in Pulmonary Arterial Hypertension

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Textbook of Pulmonary Vascular Disease

Abstract

Apoptosis (or programmed cell death) is a mechanism of cellular destruction that is essential for a variety of physiological events, such as tissue sculpturing during develop­ment and the removal of abnormal or damaged cells. However, untimely activation of this process can contribute to the pathogenesis and progression of a variety of human diseases, and pulmonary arterial hypertension is no exception. Recent evidence indicates that endothelial cell (EC) apoptosis is critically involved in the pathophysiological changes in PAH and that increased or decreased levels of apoptosis may contribute to different stages of the disease. The purpose of this chapter is to provide an overview of this rapidly evolving field and try to reconcile some of the apparent conflicts regarding the role of EC apoptosis in the initiation and progression of pulmonary hypertension. Considerable attention has been paid to the role of reduced apoptosis in other vascular cell types, particularly vascular smooth muscle cells (SMCs), which contributes to the massive medial growth and arterial remodeling characteristic of established disease, and this is reviewed in detail in other chapters. In contrast, this chapter will highlight the current concepts and controversies surrounding the role of abnormal EC growth and survival in the pathogenesis of PAH. In particular, the role of endothelial apoptosis as an initiating event in the development of PAH will be reviewed and current concepts pertaining to the emergence of hyperproliferative and ­apoptosis-resistant ECs in later stages of this disease will be discussed. This chapter also attempts to provide a unifying framework reconciling the apparent discrepancies between early apoptosis and EC cell loss which may represent one of the first events in the initiation of PAH, and the angioproliferative lesions that contribute characteristic pathological features of advanced disease.

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Authors and Affiliations

  1. Department of Medicine, University of Ottawa, Ottawa, Canada

    Duncan J. Stewart

  2. Ottawa Health Research Institute, The Ottawa Hospital, 501 Smyth Road, Ottowa, ON, K1H 8L6, Canada

    Duncan J. Stewart

Authors
  1. Rohit Moudgil
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  2. Manoj M. Lalu
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  3. Duncan J. Stewart
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Correspondence to Duncan J. Stewart .

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  1. Departments of Medicine, COMRB Rm. 3131 (MC 719), University of Illinois at Chicago, 909 South Wolcott Avenue, Chicago, 60612, Illinois, USA

    Jason X. -J. Yuan

  2. 310 Admin.Office Building (MC 672), University of Illinois at Chicago, 1737 W. Polk Street, Suite 310, Chicago, 60612, Illinois, USA

    Joe G.N. Garcia

  3. Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, 92093-0623, California, USA

    John B. West

  4. Dept. Pulmonary & Critical Care Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, 02114, Massachusetts, USA

    Charles A. Hales

  5. Department of Medicine, University of Chicago Medical Center, 5841 S. Maryland Ave., Chicago, 60637, Illinois, USA

    Stuart Rich

  6. Department of Medicine, University of Chicago School of Medicine, 5841 S. Maryland Ave., Chicago, 60637, Illinois, USA

    Stephen L. Archer

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Moudgil, R., Lalu, M.M., Stewart, D.J. (2011). Endothelial Apoptosis and Repair in Pulmonary Arterial Hypertension. In: Yuan, JJ., Garcia, J., West, J., Hales, C., Rich, S., Archer, S. (eds) Textbook of Pulmonary Vascular Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-87429-6_28

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