Abstract 17614: 6-mercaptopurine Reduces Progression of Experimentally Induced Pulmonary Arterial Hypertension by Dampening Inflammation and Inhibition of Proliferation

Rationale: Inflammation plays a crucial role in pulmonary arterial hypertension (PAH). Inflammatory cytokines stimulate proliferation of pulmonary arterial smooth muscle cells (PASMC) and endothelial cells (EC). 6-Mercaptopurine (6-MP) is a well-established immunosuppressive drug used to treat various autoimmune and chronic inflammatory diseases. Recently, we and others have shown that 6-MP not only inhibits macrophage and T cell activation, but also reduces the proliferation of SMC and EC as well as the inflammatory response of EC. Collectively, given the effects of 6-MP on inflammation, SMC and EC, we hypothesized that 6-MP may be a promising treatment of PAH. Methods: Pulmonary hypertension was induced in male Sprague-Dawley rats by a single injection of SU5416 (25 mg/kg) followed by a 4-week transient exposure to hypoxia and a 2-week normoxic re-exposure. After randomization (treatment vs. vehicle) animals were divided into two groups, receiving 6-MP (1 mg/kg) or vehicle (DMSO) in drinking water from ...