Metabolic and hormonal derangements in pulmonary hypertension: from mouse to man

Pulmonary arterial hypertension (PAH) is a complex disease with significant morbidity and mortality. Recent animal and human studies have highlighted abnormalities in regulation and metabolism of insulin, sex hormones, adipokines and lipids that may play a role in disease development. Mouse studies suggest features of the metabolic syndrome (MS) including insulin resistance, deficiencies in peroxisome proliferator-activated receptor γ and apolipoprotein E, and low adiponectin are linked to development of PAH. In humans, insulin resistance, the MS and low levels of high-density lipoprotein have been associated with PAH. In addition, abnormal metabolism of oestrogens has been demonstrated in human and animal models of PAH, suggesting an important relationship of sex hormones and pulmonary vascular disease. Improved understanding of how metabolic and hormonal derangements relate to development and progression of pulmonary hypertension may lead to better disease therapies and understanding of potential risk factors. This review will focus on the animal and human data regarding metabolic and sex hormone derangements in PAH.