The crossroads of iron with hypoxia and cellular metabolism. Implications in the pathobiology of pulmonary hypertension. Robinson Jeffrey C,Graham Brian B,Rouault Tracey C,Tuder Rubin M American journal of respiratory cell and molecular biology The pathologic hallmark of pulmonary arterial hypertension (PAH) is pulmonary vascular remodeling, characterized by endothelial cell proliferation, smooth muscle hypertrophy, and perivascular inflammation, ultimately contributing to increased pulmonary arterial pressures. Several recent studies have observed that iron deficiency in patients with various forms of PAH is associated with worsened clinical outcome. Iron plays a key role in many cellular processes regulating the response to hypoxia, oxidative stress, cellular proliferation, and cell metabolism. Given the potential importance of iron supplementation in patients with the disease and the broad cellular functions of iron, we review its role in processes that pertain to PAH. 10.1165/rcmb.2014-0021TR

Iron Deficiency in Pulmonary Arterial Hypertension: A Deep Dive into the Mechanisms. Quatredeniers Marceau,Mendes-Ferreira Pedro,Santos-Ribeiro Diana,Nakhleh Morad K,Ghigna Maria-Rosa,Cohen-Kaminsky Sylvia,Perros Frédéric Cells Pulmonary arterial hypertension (PAH) is a severe cardiovascular disease that is caused by the progressive occlusion of the distal pulmonary arteries, eventually leading to right heart failure and death. Almost 40% of patients with PAH are iron deficient. Although widely studied, the mechanisms linking between PAH and iron deficiency remain unclear. Here we review the mechanisms regulating iron homeostasis and the preclinical and clinical data available on iron deficiency in PAH. Then we discuss the potential implications of iron deficiency on the development and management of PAH. 10.3390/cells10020477

Iron deficiency in pulmonary arterial hypertension: a potential therapeutic target. Rhodes C J,Wharton J,Howard L,Gibbs J S R,Vonk-Noordegraaf A,Wilkins M R The European respiratory journal Iron deficiency is known to be common and detrimental in chronic left heart failure, where parenteral iron treatment has been shown to improve exercise capacity, New York Heart Association functional class and patient wellbeing. There is now increasing interest in the role of iron in the natural history of pulmonary arterial hypertension (PAH). Iron availability influences the pulmonary vasoconstrictor response to hypoxia and accumulating evidence indicates that iron deficiency is prevalent in idiopathic and heritable forms of PAH, iron status being related to exercise capacity, symptoms and poorer survival in patients with idiopathic PAH (IPAH). Potential mechanisms behind iron deficiency in IPAH include inhibition of dietary iron uptake by the master iron regulator hepcidin. High hepcidin levels underlie the anaemia of chronic disease. Possible stimuli of the observed high levels of hepcidin in IPAH include dysfunctional bone morphogenetic protein receptor type II signalling and inflammation. Iron status may influence outcomes through modulation of the pulmonary circulation as well as myocardial and skeletal muscle function. Two parallel studies, from our centre (Hammersmith Hospital, London, UK) and others in the UK and Amsterdam (the Netherlands), investigating the safety and potential benefit of iron supplementation in patients with PAH are currently under way. 10.1183/09031936.00037711