Objective: Pulmonary arterial hypertension is characterized by smooth muscle cell hyperproliferation. We previously showed that the ?-3 fatty acid DHA reduces primary human pulmonary artery smooth muscle cell (hPASMC) proliferation via the induction of ER stress and ultimately apoptosis. Heme oxygenase-1 (HO-1) was found to be markedly up-regulated in DHA treated hPASMC. The aim of my diploma thesis was to investigate the impact of HO-1 on DHA mediated effects in hPASMC.Methods: Primary hPASMC were isolated from human central pulmonary arteries from patients undergoing lung surgery. Gene induction on mRNA and protein level was determined by quantitative PCR and Western blots, respectively. ROS generation and apoptosis was measured with fluorescent activated cell sorting (FACS). Proliferation was quantified with 3H-thymidine incorporation assays.Results: DHA induced HO-1 in hPASMC dose-and time dependently via the generation of reactive oxygen species (ROS). DHA mediated ROS generation resulted in ER stress, apoptosis and inhibition of hPASMC proliferation. Knock down of HO-1 with HO-1 silencing RNA heightened ROS generation, prolonged the ER stress response and increased apoptosis compared to controls. Knock down of HO-1 did not alter cell proliferation in DHA treated cells compared to controls. However, hemin treatment inhibited hPASMC proliferation, most likely via HO-1 induction.Conclusions: DHA induces HO-1 by the generation of ROS. HO-1 is cytoprotective and attenuates DHA induced ROS generation, ER stress and apoptosis. However, oxidative stress induced by in vitro DHA incubation exceeds the anti-oxidative capacity of HO-1. The effect of HO-1 on hPASMC proliferation is dependent on the properties of the HO-1 inducer. Hemin treatment induces HO-1 dependent inhibition of hPASMC proliferation. The cytoprotective and anti-proliferative properties of HO-1 highlight HO-1 as an inducible target enzyme for the prevention and therapy of cardiovascular disease.