Small Artery Research
Maintenance of normal peripheral vascular resistance and perfusion of vital organs depends on the structure and contractile tone of small arteries within the vasculature. Changes in these properties of small blood vessels lead to cardiovascular disease.
Researchers within the Vascular Biology group are investigating the mechanisms that regulate small artery function in health and disease. The main areas of our research and the investigators involved are detailed below.
Obesity and small artery function
Both hypertension and diabetes are particularly prevalent in obese individuals. There is a layer of fat cells that surround small arteries and in health it secretes a number of factors such as adiponectin that relax the circulation.
In obesity there is inflammation, increased oxidative stress and a loss of such adipokines leading to increased contractility, a rise in blood pressure glucose intolerance and dyslipidaemia.
In the Institute, the Vascular Biology Group has Principal Investigator's researching the physiology of arterial contraction, the role of perivascular fat on vascular tone and the circulatory consequences of these diseases such as coronary artery atherosclerosis, they are as follows:
(Image: Perivascular adipose tissue surrounding a blood vessel)
Disorders of the vasculature such as atherosclerosis and hypertension are associated with aberrant behavior of smooth muscle cells, and our focus is directed at determining the mechanisms by which the smooth muscle cells of the vasculature regulate their contractility and adapt to the mechanical stresses of their surrounding environment.
In the Institute, the Vascular Biology Group has Principal Investigator's researching the signalling pathways regulating the actin cytoskeleton and the role of lipid second messengers in vascular smooth muscle function:
(Image: Vascular smooth muscle cell with actin cytoskeleton labelled red and focal adhesion sites labelled green)
Understanding the mechanisms of blood vessel development has implications in a number of human disease conditions such as cardiovascular disease, eye disease and cancer where abnormal vessel growth plays a crucial part in pathogenesis.
Insights in the cellular signalling pathways regulating angiogenesis are essential for designing novel therapeutic strategies.
We are particularly interested in investigating a secreted small ligand called apelin and its role in diabetic retinopathy using mouse as the model system.
(Image: Retinal vasculature with astrocytes labelled in green)
Ion Channels and Calcium Signalling
The aim of the Greenstein/Nelson group at the University of Manchester is to understand how perivascular adipose tissue, smooth muscle cells and endothelial cells communicate ("vascular crosstalk") to control the function of resistance-sized peripheral arteries.
We do this by studying the roles of ion channels and calcium signaling. Approaches cover the spectrum from molecular, cellular, intact tissue, whole organ and in vivo (local Cerebral blood flow, blood pressure). A number of genetic mouse models are used to unravel control mechanisms. Relevant ion channels in smooth muscle and endothelium are being explored, including voltage-dependent calcium channels, inward rectifier potassium channels, calcium-sensitive BK, IK, SK channels, voltage-dependent potassium channels, TRPV4 channels and ryanodine receptor channels.