Inflammation, Growth Factors, and Pulmonary Vascular Remodeling

Paul M. Hassoun, Luc Mouthon, Joan A. Barberà, Saadia Eddahibi, Sonia C. Flores, Friedrich Grimminger, Peter Lloyd Jones, Michael L. Maitland, Evangelos D. Michelakis, Nicholas W. Morrell, John H. Newman, Marlene Rabinovitch, Ralph Schermuly, Kurt R. Stenmark, Norbert F. Voelkel, Jason X.J. Yuan, Marc Humbert

Research output: Contribution to journalReview article

473 Scopus citations

Abstract

Inflammatory processes are prominent in various types of human and experimental pulmonary hypertension (PH) and are increasingly recognized as major pathogenic components of pulmonary vascular remodeling. Macrophages, T and B lymphocytes, and dendritic cells are present in the vascular lesions of PH, whether in idiopathic pulmonary arterial hypertension (PAH) or PAH related to more classical forms of inflammatory syndromes such as connective tissue diseases, human immunodeficiency virus (HIV), or other viral etiologies. Similarly, the presence of circulating chemokines and cytokines, viral protein components (e.g., HIV-1 Nef), and increased expression of growth (such as vascular endothelial growth factor and platelet-derived growth factor) and transcriptional (e.g., nuclear factor of activated T cells or NFAT) factors in these patients are thought to contribute directly to further recruitment of inflammatory cells and proliferation of smooth muscle and endothelial cells. Other processes, such as mitochondrial and ion channel dysregulation, seem to convey a state of cellular resistance to apoptosis; this has recently emerged as a necessary event in the pathogenesis of pulmonary vascular remodeling. Thus, the recognition of complex inflammatory disturbances in the vascular remodeling process offers potential specific targets for therapy and has recently led to clinical trials investigating, for example, the use of tyrosine kinase inhibitors. This paper provides an overview of specific inflammatory pathways involving cells, chemokines and cytokines, cellular dysfunctions, growth factors, and viral proteins, highlighting their potential role in pulmonary vascular remodeling and the possibility of future targeted therapy.

Original languageEnglish (US)
Pages (from-to)S10-S19
JournalJournal of the American College of Cardiology
Volume54
Issue number1 SUPPL. 1
DOIs
StatePublished - Jun 30 2009
Externally publishedYes

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Keywords

  • growth factors
  • inflammation
  • pulmonary vascular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hassoun, P. M., Mouthon, L., Barberà, J. A., Eddahibi, S., Flores, S. C., Grimminger, F., Jones, P. L., Maitland, M. L., Michelakis, E. D., Morrell, N. W., Newman, J. H., Rabinovitch, M., Schermuly, R., Stenmark, K. R., Voelkel, N. F., Yuan, J. X. J., & Humbert, M. (2009). Inflammation, Growth Factors, and Pulmonary Vascular Remodeling. Journal of the American College of Cardiology, 54(1 SUPPL. 1), S10-S19. https://doi.org/10.1016/j.jacc.2009.04.006