Professor Ann Canfield (BSc, PhD) - research
Molecular and Cellular mechanisms underpinning Vascular Calcification and Angiogenesis
Vascular calcification is a common complication of many diseases including atherosclerosis, diabetes, renal disease, hypertension, vein graft failure and calciphylaxis. Recent studies have shown that there is a strong association between the presence of vascular calcification and adverse clinical events such as myocardial infarction and stroke. However, little is known about how the deposition of mineral in vessels is controlled. We have shown that vascular pericytes have multi-lineage potential and can differentiate into osteoblasts and chondrocytes in vitro and in vivo. We have also shown that these cells can deposit a calcified matrix resembling that found in calcified atherosclerotic plaques, suggesting that pericytes may mediate, at least in part, vascular calcification. We have recently demonstrated that several genes that are implicated in the pathological calcification of arteries, namely matrix Gla protein, Axl receptor tyrosine kinase and HtrA1 serine protease are all differentially expressed during pericyte differentiation. We are currently using molecular, cellular and biochemical approaches to elucidate the mechanisms by which each of these proteins regulates calcification. In time, this integrated programme of research will provide important insights into the pathogenesis of vascular calcification and may identify potential targets for the therapeutic manipulation of this event.
Angiogenesis is the formation of new blood vessels from an existing vascular bed. It is of fundamental importance in many physiological and pathological conditions, including embryonic development, wound healing, atherosclerosis, diabetic retinopathy, psoriasis and tumour growth and metastasis. Angiogenesis is a complex process involving changes in endothelial cell phenotype, extracellular matrix remodelling and stabilisation of the newly formed blood vessels. We are currently employing a multidisciplinary approach to define the roles of specific angiogenic factors and matrix proteins in regulating endothelial cell-pericyte interactions that are crucial for vessel stabilisation. We aim to translate this work into the development of novel anti-angiogenic and pro-angiogenic strategies for the treatment of diseases characterised by abnormal vascularisation.