Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease

Evgeny A. Zemskov, Qing Lu, Wojciech Ornatowski, Christina N. Klinger, Ankit A. Desai, Emin Maltepe, Jason X.J. Yuan, Ting Wang, Jeffrey R. Fineman, Stephen M. Black

Research output: Contribution to journalReview article

5 Scopus citations

Abstract

Significance: Oxidative stress in the cell is characterized by excessive generation of reactive oxygen species (ROS). Superoxide (O2-) and hydrogen peroxide (H2O2) are the main ROS involved in the regulation of cellular metabolism. As our fundamental understanding of the underlying causes of lung disease has increased it has become evident that oxidative stress plays a critical role. Recent Advances: A number of cells in the lung both produce, and respond to, ROS. These include vascular endothelial and smooth muscle cells, fibroblasts, and epithelial cells as well as the cells involved in the inflammatory response, including macrophages, neutrophils, eosinophils. The redox system is involved in multiple aspects of cell metabolism and cell homeostasis. Critical Issues: Dysregulation of the cellular redox system has consequential effects on cell signaling pathways that are intimately involved in disease progression. The lung is exposed to biomechanical forces (fluid shear stress, cyclic stretch, and pressure) due to the passage of blood through the pulmonary vessels and the distension of the lungs during the breathing cycle. Cells within the lung respond to these forces by activating signal transduction pathways that alter their redox state with both physiologic and pathologic consequences. Future Directions: Here, we will discuss the intimate relationship between biomechanical forces and redox signaling and its role in the development of pulmonary disease. An understanding of the molecular mechanisms induced by biomechanical forces in the pulmonary vasculature is necessary for the development of new therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)819-842
Number of pages24
JournalAntioxidants and Redox Signaling
Volume31
Issue number12
DOIs
StatePublished - Oct 20 2019

Keywords

  • biomechanical forces
  • cyclic stretch
  • mitochondria
  • pulmonary disease
  • redox regulation
  • shear stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Zemskov, E. A., Lu, Q., Ornatowski, W., Klinger, C. N., Desai, A. A., Maltepe, E., Yuan, J. X. J., Wang, T., Fineman, J. R., & Black, S. M. (2019). Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease. Antioxidants and Redox Signaling, 31(12), 819-842. https://doi.org/10.1089/ars.2018.7720