Harnessing the body’s natural defences against blood vessel damage

The role of double-stranded RNA in pulmonary vascular remodelling

Pulmonary arterial hypertension (PAH) is a devastating condition caused when the blood vessels in the lung become progressively narrower. This causes increased blood pressure in the lungs and can lead to heart failure. This abnormal narrowing of blood vessels involves the growth of muscle cells in the vessel wall and is called ‘blood vessel remodelling’. However, the body has some natural defence systems to protect against blood vessel damage. Specifically, Dr Thompson has discovered that a damage-sensing defence molecule, called TLR3, can protect against PAH in mice. In this fellowship, he aims to understand how TLR3, and the molecules that switch it on, work. This knowledge could lead to the development of new treatments for PAH in the future. Dr Thompson is focussing on particular molecules that switch on TLR3 called double-stranded RNA (dsRNA). He has already shown that these can protect against lung blood vessel remodelling in rats with PAH. Building on this, he is now investigating whether other dsRNA sensors also regulate pulmonary vascular remodelling. These studies will be carried out in animal models of PAH and Dr Thompson will also then use lung tissue samples from patients with PAH to confirm his findings in humans. This research will reveal crucial insights into molecular processes that control blood vessel remodelling that could be used in the design of urgently needed new treatments for this condition.