Novel treatments of fibrosis for hypertensive heart disease

One of the most recognised risk factors for cardiovascular disease is hypertension. Cardiac fibrosis is at the centre of many pathological conditions and a reduction in cardiac fibrosis is now seen as a key factor to improved cardiovascular outcomes. However, there are few treatments that directly ameliorate fibrosis associated with hypertensive heart disease, which may lead to heart failure. Small cardioprotective effects are seen with ACE inhibitors or AT1 receptor antagonists, but these drug classes cannot be given in combination because the adverse effects (hypotension, renal failure) outweigh their potential ability to maximise organ remodelling. Our group has developed the first highly selective series of compounds that stimulate AT2 receptors, part of the ‘cardioprotective arms’ of the renin-angiotensin-system (RAS). This project aims to characterise these compounds either encapsulated in novel injectable hydrogels or as orally-acting derivatives.