SMART

Small Artery Remodelling

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 Obiettivo del progetto (Objective)

'Cardiovascular diseases are the leading cause of death and disability in the European population and represent a great burden of suffering and costs. Their complex etiology originates from different pathological stimuli and involves different cell types, resident in the vascular wall or infiltrating from the blood. The adaptation of the vasculature to physiological and pathophysiological forces depends on both the communication between its cellular components and their interaction with the extracellular matrix (ECM). When subjected to enhanced stretch, cyclic mechanical strain, or shear stress, blood vessels undergo typical transformations in wall shape that are always associated with alterations of the ECM and cellular composition, collectively described as vascular remodelling. Remodelling processes occur specifically in small arteries and arterioles, which show extreme changes in their size and function (microvascular remodelling). This is especially the case in hypertensive or diabetic patients, and contributes to a vicious cycle resulting in organ dysfunction and progression of vascular disease. A multidisciplinary approach is required to better understand vascular remodelling processes. We propose an interdisciplinary ITN to promote excellence in vascular biology, with focus on small vessels/arteries and their ECM. This will enhance the interaction between 8 academic groups and one SME in 7 European countries, specialized in physiology, signalling mechanisms, cell-cell and cell-matrix interactions in vascular endothelium and smooth muscle, as well as in drug discovery and development. The ITN will provide a specialized training ground by connecting investigations of the biology of vascular cells and their surrounding ECM in an innovative manner. It will therefore promote the careers of young investigators by specialising them in a field of vascular biology with a great potential for the future.'

Introduzione (Teaser)

Cardiovascular disease is a leading cause of death in Europe. Understanding the molecular and cellular events that drive vascular remodelling in health and disease would help identify novel therapeutic targets.

Descrizione progetto (Article)

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' (http://www.smallartery.eu/ (SMART)) 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.