Oestrogenic contribution of adipose tissue in obesity-associated pulmonary arterial hypertension
Sofia Laforest, Strathclyde Institute of Pharmacy and Biomedical Sciences, Edinburgh
Pulmonary arterial hypertension (PAH) is a disease involving a gradual increase in pulmonary vascular resistance due to the occlusion of small pulmonary arteries, ultimately leading to right ventricular heart failure and death. Contrary to other cardiovascular diseases, the prevalence of PAH is skewed towards women. This suggests a pathogenic role of steroid hormones. Our group has focused on the role of oestrogen metabolites in PAH. In a mouse model, we established that 16αOHE1 excretion from fat contributes to the pathogenesis of PAH. 16αOHE1 is a potent mitogen in pulmonary artery smooth muscle cells. Injection of this metabolite in mice promotes PAH.
The overarching aim of this project is to assess the contribution of the visceral adipose tissue to the pool of steroids, especially oestrogens, in obesity-associated PAH. To address this, it is necessary to establish methods to assess the steroid profile in murine adipose tissue and evaluate if it varies between sex in experimental PAH. BMPR2 mutation are responsible for most heritable PAH cases; BMPR2 is a cell receptor that protects against proliferation.
Therefore, I plan to study the sex difference in a preclinical model of a heterozygous knock-in Bmpr2+/R899X human mutation in lean and obese animals.
Grant awarded: £4,976.75