Multilevel omics: A next step on the way to understanding pulmonary arterial hypertension?

Pulmonary arterial hypertension (PAH) remains a major cause of morbidity and mortality despite continuous efforts to increase our understanding of the underlying pathophysiology.1 As a matter of fact, little has changed in terms of our ability to treat this deadly disease since the introduction of the first vasodilator treatment two decades ago.2 3 Although three different classes of drugs are currently available, all converge on the same downstream event (ie, vasodilation). The fact that mortality is still high despite current therapy suggests that there are hitherto unknown mechanisms that determine the outcome. Omic approaches provide an unbiased method, and—being both inclusive and hierarchical—omics may help to prioritise candidate targets for development of novel drug classes. In the current issue of Thorax ,4 Harbaum et al have combined metabolomic and proteomic studies to assess whether a specific lipoprotein composition is associated with clinical endpoints in patients with PAH. Using nuclear MR spectroscopy, 105 different lipoproteins were measured in the plasma of patients with idiopathic or hereditary PAH and correlated with survival. The study demonstrated association of PAH survival with three lipoproteins of the high-density lipoprotein (HDL) subclass 4, of which HDL-4-apolipoprotein A-2 (HDL-4-Apo A-2) showed the strongest association. Higher levels of HDL-4-Apo A-2 were …