Vascular injury & repair
Vascular injury & repair
Cardiovascular disease remains the biggest single cause of death and disability in many countries, accounting for 160,000 deaths each year in the UK, 42,000 of which occur in people below the age of 75. However, an improved understanding of cardiovascular disease has led to better treatments, with death rates in the UK declining by more than three quarters in the last 50 years (BHF heart statistics). Despite this, many aspects of cardiovascular disease pathogenesis need clarification to continue the improvement of preventative and treatment strategies. The cardiovascular group comprises a collaboration of clinical and basic scientists with an interest in the mechanisms involved in arterial narrowing (atherosclerosis, neointimal proliferation) and vascular growth (vasculogenesis, arteriogenesis, angiogenesis) and cardiac injury/ repair. This interaction allows investigations to range “from molecule to man” using combinations of molecular and cellular biology, preclinical testing and clinical investigations. Improving our understanding of cardiovascular remodelling should enable the development of new treatments for clinically-significant conditions, including coronary artery disease, stroke, myocardial infarction and critical limb ischaemia. Considerable interest currently centres on the use of cell administration to stimulate angiogenesis in ischaemic tissues. Challenges include identifying (with the development of new imaging techniques and identification of novel biomarkers) and treating the vulnerable, rupture prone lesions that are implicated in cardiovascular morbidity and mortality. Much effort is focussed on the use of state-of-the-art imaging techniques to improve detection and analysis of unstable lesions and to demonstrate the impact of treatment on these plaques.
Neointimal Proliferation/ Atherosclerosis
The Cardiovascular group has extensive experience in this area, with strong research themes investigating the impact of particulate air pollution, hormones (glucocorticoids, androgens) and endothelins on arterial narrowing and rupture. New treatments have been assessed, including the use of viral vectors for targeting vascular injury. More recent research addresses the influence of hydrogen sulphide, miRNAs and lncRNAs on lesion formation. An example of an atherosclerotic plaque is shown below:
The growth of new blood vessels is vital to the developing foetus and has specific roles in the adult. Alterations in angiogenesis can contribute to disease development (for example in atherosclerosis, retinopathy) but stimulation of new vessel formation has potential for the treatment of ischaemic disease (eg myocardial infarction, critical limb ischaemia). Research within the group addresses the influence of hormones (glucocorticoids, androgens) and trichoplein on neovascularisation. Cell tracking studies are also addressing the possibility that clonal expansion of endothelial cells is responsible for generation of new vascular networks (and for arterial repair).
Pre-clinical models have been used extensively to investigate the healing mechanisms (incorporating acute and chronic inflammatory responses and the angiogenic growth of new blood vessels) following myocardial infarction. This includes clarifying the mechanisms enabling injured neonatal hearts to regenerate which are lost soon after birth.
Considerable interest currently centres on the potential for cell (particularly stem cell) therapies for use in the treatment of vascular disease; for example by targeting areas of arterial injury and “reseeding” with healthy cells; or by using cell administration to stimulate new vessel growth in ischaemic tissues. The Cardiovascular group has established research interests in the regenerative potential of perivascular cells (pericytes, adventitial cells) and endothelial progenitor cells.
There is a considerable need to development biomarkers to improve diagnosis of myocardial infarction and identification of patients at risk of lesion rupture. Scientists in the Cardiovascular group have led the development of novel biomarkers (high sensitivity troponin) that help identify patients who have suffered a heart attack.
Staff in the group have developed novel imaging technologies to help identify, analyse and understand cardiovascular remodelling in vivo. Techniques including MRI, PET/CT, ultrasound have been used in both pre-clinical models and in patients, providing a better understanding of the time-dependent development of cardiovascular disease and promising methods for identifying vulnerable lesions. Imaging techniques have also been used to track the fate of cells administered to modulate arterial injury/ angiogenesis.