Effect of Carnosine on Walking Endurance in Patients with Peripheral Vascular Disease

Project: Research

Project Description

The prevalence of peripheral vascular disease (PVD) is high and increases with age, diabetes and smoking. Available drugs have limited effects. Exercise alleviates symptoms and increases walking endurance in PVD patients, however, compliance is poor due to pain. Hence, there is a need to identify and test safe strategies that are synergistic with exercise to improve the walking endurance in this growing patient population.
Post-natal vessel growth, which would be beneficial in PVD, is initiated by the activation of transcription factor HIF-1α. This leads to the expression of angiogenic genes that are essential to promote mobilisation of endothelial progenitor cells. HIF-1α is targeted for degradation through the activity of prolylhydroxylase (PHD), a process that requires iron. Recent studies show that metal chelators and pharmaceutical inhibitors of PHDs can prevent degradation of HIF-1α and promote revascularisation.
Carnosine, a naturally occurring dipeptide in muscle with chelating properties and an excellent safety profile, is currently used in sport to increase exercise capacity. We and others have demonstrated cardiometabolic benefits of carnosine in humans and shown that they are mediated via reduction in chronic low-grade inflammation, oxidative stress and advanced glycation endproducts. The same mechanisms contribute also to the pathophysiology of PVD. We hypothesise that chelation of iron by carnosine inactivates PHDs and increases HIF1- stabilisation and therefore enhances angiogenesis in the ischaemic muscle.
The crucial next step is a rigorous clinical trial to establish efficacy of carnosine in patients with PVD. We aim to determine if carnosine, in addition to home-based exercise intervention, can improve walking endurance of patients with PVD compared to placebo and identify the mechanisms involved. If positive, this will have important clinical implications for treatment of PVD - through safe, readily available, and low-cost intervention.
Short titleCarnosine for Peripheral Vascular Disease
StatusActive
Effective start/end date1/07/1930/06/20