Effect of chronic hypoxia and selective knock out of smooth muscle NFATc3 on gene expression in pulmonary arteries

CH causes perivascular inflammation, enhanced pulmonary arterial constriction and remodeling leading to the development of pulmonary hypertension. Pulmonary hypertension is a debilitating disease with a high mortality rate. CH develops in patients with chronic obstructive pulmonary disease (COPD), sleep apnea or people living at high altitude. Both COPD and sleep apnea are very prevalent and pulmonary hypertension develops in a large % of COPD and sleep apnea patients. The molecular mechanisms that underlie the development of CH-induced pulmonary hypertension are far from clear. We have previously demonstrated that CH activates the Ca2+/calcineurin-regulated transcription factor NFATc3 in PASMC and that NFATc3 is required for CH-induced pulmonary hypertension in mice. Although this work was the first to identify a role for this transcription factor in an experimental model of pulmonary hypertension, since a conventional whole animal KO was used it is unknown if PASMC NFATc3 contributes to CH-induced PH. Furthermore, the genes regulated by NFATc3 in PASMC under control and CH conditions are largely unknown.

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