Oh NO! Loss of PHD2 leads to “radical” changes in the lung vasculature

The role for endothelial nitric oxide synthase (eNOS) in the pathogenesis of pulmonary arterial hypertension (PAH) is complex and multifaceted. Initially, it was reported that eNOS expression was profoundly reduced in the lung vasculature of patients with PAH [1]. The pairing of this reduction with a marked upregulation of endothelin-1 [2] evoked a straightforward and attractive paradigm of endothelial dysfunction in PAH in which an imbalance in the production of vasodilator and vasoconstrictor factors led to abnormal pulmonary vasoconstriction and arterial remodelling. However, subsequent studies were unable to confirm downregulation of lung vascular eNOS in similar PAH patient populations, and instead showed no change or a robust upregulation [3, 4], suggesting that increased nitric oxide (NO) production may in fact be involved in arterial remodelling in this disease via some unknown mechanism. The PHD2 deficient mouse model of nitrative stress provides an excellent opportunity to explore these important relationships, potentially providing critical insight into the pathogenesis of PAH https://bit.ly/3r66aBF