Pulmonary Vasculature Redox Signaling in Health and Disease

Michael Thompson, Rodney D. Britt, Christina M. Pabelick, Y. S. Prakash, Thompson, Michael, Britt, Rodney D., Pabelick, Christina M., Prakash, Y. S.

Hypoxia is recognized as a contributor to pulmonary vascular diseases such as pulmonary hypertension. Hypoxia-induced inflammatory changes can enhance structural and functional changes in pulmonary artery (PA) in the context of PH. Accordingly, understanding how hypoxia and inflammation are linked in the context of pulmonary artery structure and function could be relevant towards development of novel therapies for PH. In this regard, factors such as thymic stromal lymphopoietin (TSLP), an inflammatory cytokine, and brain-derived neurotrophic factor (BDNF), a neurotrophin, have been found critical for nonvascular systems such as airway and asthma. While TSLP canonically affects the immune system, in nonvascular systems, noncanonical effects such as altered [Ca(2+)]i and cell proliferation have been noted: aspects also relevant to the PA, where there is currently little to no data. Similarly, better known in the nervous system, there is increasing evidence that BDNF is locally produced by structural cells of the airway and can contribute to asthma pathophysiology. In this chapter, we summarize the potential relevance of factors such as TSLP and BDNF to the PA and in the context of hypoxia influences towards development of PH. We focus on cell sources and targets such as PA endothelial cells (PAECs) and smooth muscle cells (PASMCs), and the effects of TSLP or BDNF on intracellular Ca(2+) responses to vasoconstrictor agonist, cell proliferation, and potential signaling cascades involved.