Heart failure (HF) with preserved ejection fraction (HFpEF) is increasing in prevalence and there are NO evidence-based effective therapies. The pathophysiology that underpins HFpEF is complex due to multiple comorbidities such as obesity, hypertension, & aging having an elevated oxidative stress status. Oxidative stress activates apoptosis signal-regulating kinase 1 (ASK1) which is the key driver of the development of HFpEF phenotype.
Our project team is at the forefront of HFpEF research internationally. Building on our previous HF research, we have demonstrated a novel small molecule ASK1 inhibitor, G226, can effectively attenuate cardiac remodeling both in vitro & in vivo with low toxicity. Thus, this proposal will investigate the therapeutic potential of G226 in both young & aged mice with high-fat diet-fed & angiotensin II infusion-induced HFpEF models. Studies will be performed to demonstrate the potential of G226 in the prevention and treatment of HFpEF in these animal models which will lead to a novel strategy for HFpEF management.
Last updated17 January 2023