Targeting the NLRP3 inflammasome in the treatment of pulmonary hypertension

Pulmonary hypertension (PH) is an incurable disease and a major cause of death and illness throughout the world. Whilst there has been advancement in the treatment of PH, current treatment is not optimal, with 5 year survival of ~50%. New therapeutic strategies are urgently needed. Our research group has recently demonstrated that macrophages and, in particular the NLRP3 inflammasome, are associated with pathological pulmonary and cardiac remodelling in pulmonary hypertension. Hence, we are interested in studying the impact of NLRP3 inflammasome inhibition of the development of PH and the associated end-organ damage. Project: Assessing the therapeutic utility of pharmacological targeting the NLRP3 inflammasome to protect against chronic hypoxia-induced pulmonary hypertension. Techniques: Techniques that will be used during this project include establishing a 4-week mouse model of chronic hypoxia-induced pulmonary hypertension, and involve the measurement of blood pressure and ex vivo assays to assess vascular function (myography), detect inflammation (RT-PCR, superoxide detection), collagen generation (zymography, immunohistochemistry) and lung histology.