How gases boost blood vessel growth in peripheral arterial disease

Investigation of the redox-dependent regulation of the vascular angiogenic response following ischemia

Dr Alison Brewer and her colleagues at King’s College London are studying peripheral artery disease, or PAD, where the blood supply to tissues in the limbs is insufficient. There is currently no effective treatment for PAD and, in severe cases, the only treatment is amputation. The body’s normal response to low blood supply is to promote the growth of new blood vessels to meet oxygen demand. We know certain cells of the circulatory system produce gases called H2S, CO and NO that encourage new blood vessel growth. But to be effective, these gases must be made close to the place they are needed at the right time, so the enzymes that make them must be tightly controlled. Dr Brewer has identified molecular pathways that increase H2S and CO production. In this project, she will test, both in cells and in mice, whether these pathways are normally activated in response to a lack of oxygen, and whether they can boost blood vessel growth and blood flow. She will also work out how another molecule called Nox4 increases when oxygen supply to tissues is reduced. This research may identify molecular pathways that reveal new ways to prevent or treat PAD and reduce the need for amputations.