Artery remodelling
Although the pathological stimuli may vary, arteries in cardiovascular disease are subjected to different types of stress such as elevated pressure. This causes them to undergo changes in wall shape as a result of alterations in the extracellular matrix and in the composition of vascular cells. This process is known as vascular remodelling. In diabetic or hypertensive individuals, it can lead to cardiovascular disease. The expertise of the EU-funded 'Small artery remodelling' (SMART)(opens in new window) consortium focused on the biology of vascular cells and their surrounding extracellular matrix in health and disease. The main scientific objective was to elucidate the molecular mechanisms of cell-matrix and cell-cell interactions which take place during small artery remodelling. Small arteries branch out from the aorta and other arteries and are responsible for the oxygenation of all tissues in the body. SMART researchers were interested to see how ageing and low oxygen supply can affect vascular remodelling. They discovered that hypoxia hampered artery formation and that ageing was associated with increased artery size and greater extracellular matrix composition. In addition, they looked at how the laminin family of basal membrane proteins affects the arterial response to shear and pressure. They went on to further dissect the process of vascular remodelling with respect to the rearrangements that take place. They unravelled novel mechanisms regulating differentiation and growth of vascular cells and singled out key proteins. Analysis of small artery remodelling in hypertensive rat models provided important insight about gene expression, artery structure and biomechanical properties, as well as endothelial function during disease. Another key event in the remodelling process is the recruitment of stem cells to the damaged vessels. Scientists found that VEGF signalling regulated their differentiation into endothelial cells and identified microRNA-21 as the key regulator of this process. The SMART study put together important pieces in the puzzle of vascular remodelling and identified several factors that could serve as potential therapeutic targets. This information could help reduce acute events such as stroke and myocardial infarction in vulnerable patients.
