Head – Jaye Chin-Dusting
This group studies the relationship between blood vessels and cardiovascular disease, in particular the innermost layer of blood vessels, known as the endothelium.
Jaye and her team of researchers have significantly built on the discovery more than 25 years ago that the endothelium – the innermost layer of the blood vessels, separating the blood from the muscle - was not a passive barrier as it had been assumed but in fact a very active structure in its own right. The discovery that nitric oxide was released by the endothelium, expanding blood vessels, during activity was significant. During exercise the heart needs more oxygen and pumps harder. As a result the blood flows harder and the sheer stress of movement along the endothelium triggers this release of nitric oxide. This release of nitric oxide expands the muscles allowing more oxygen to go to the heart as is needed. When there is disease, however – hypertension, diabetes, heart failure – there is impairment of the endothelium and the release of nitric oxide is impaired. Without its release there is not the necessary dilation and sometimes there is a restriction of the vessel, causing angina. The lack of nitric oxide can limit the carriage of oxygen to the heart, resulting in heart damage. From this starting point, the Vascular Pharmacology team have investigated cellular mechanisms in a range of cardiovascular diseases. It was the work of this lab that established a new form of treatment for people with cirrhosis, or scarring, of the liver. The observation that cirrhotic patients have exactly the opposite physiological profile to patients with CVD, for example low blood pressure as opposed to high was taken further by Jaye and her team. While this opposite profile had been noted, Jaye’s lab was the first to look at the role of nitric oxide in these two patient groups, and whether there was an overproduction of nitric oxide in the cirrhotic patients responsible for the low blood pressure and other complications.
They hypothesised that the scarring of the liver in cirrhotic patients interfered with the process of blood cleansing that occurs in the portal system, where blood is transferred from the gut to the liver. Cirrhosis congested this flow and new blood vessels formed to compensate, allowing the transfer of blood from the gut directly into the systemic circulation, bypassing an important cleansing process. In patients with alcohol induced cirrhosis, diet is often poor, resulting in an increase in bacteria levels in the gut that in turn compounds the effects of liver dysfunction. The Vascular Pharmacology team surmised that the high level of end toxins in this group – toxins released from cells - was responsible for the copious release of nitric oxide, as these toxins switched on an enzyme triggering the inappropriate production of this gas in cirrhotic patients. To test their hypothesis, they recruited a group of cirrhotic patients and treated them with an antibiotic, to great effect. The successful outcomes for liver patients with a treatment model developed at a cardiovascular institute is a prime example of how the work of Baker researchers feeds into the improvement of health in the community on many different levels.
Postdoctoral researcher Kevin Woollard has been working with the lab on the effect of the endothelium on the blood, a new direction for Jaye’s team. While previously work has been focused on the influence of the endothelium on muscle constrictions and dilations, research is now turning to the release of nitric oxide into the blood. When the endothelium is damaged blood cells start to stick together forming plaques. Kevin’s research is looking at the production of “sticky” proteins during endothelial cell damage. These proteins, only expressed in cell injury, are of interest because their presence in the blood at high levels is understood to be a marker of disease. Kevin and the Vascular Pharmacology lab are particularly interested in the protein selectin, and research is focusing on the discovery that selectin is not merely an inactive biomarker but a significant contributor to disease in its own right and as such, drug treatments for disease indicated by its presence can focus on switching off the effects of this protein.