A team of researchers has developed a novel probe that enables earlier detection of cardiovascular disease, one of the leading worldwide causes of mortality.
The researchers, from the Department of Chemistry and the National Lung and Heart Institute at Imperial College London, have manufactured a glowing probe that is proficient in distinguishing an enzyme that is the precursor to cardiovascular disease – potentially improving patient outcomes.
The innovative probe can rapidly and accurately detect an enzyme that is prominent in modified E. coli cells and linked to issues that cause strokes and blood clots – some of the deadliest implications of cardiovascular disease. Their research is funded by the British Heart Foundation (BHF) and published in the Journal of the American Chemical Society.
What causes cardiovascular disease?
One of the leading causes of a litany of conditions associated with cardiovascular disease is atherosclerosis – the building up of plaque in the arteries that consequently results in strokes and coronary artery disease. If atherosclerosis further advances, it can initiate intraplaque haemorrhages (IPHs), a process where portions of the plaque separate from the artery wall, creating additional vulnerable plaques and blood clots that restrict blood flow to the brain and heart, resulting in strokes and chronic diseases.
The neoteric chemical probe can accurately detect rising levels of the enzyme that correlates with IPHs and even preceding plaque instabilities, meaning the implementation of such a device will accurately provide an early warning system for these life-threatening events.
Nicholas Long, the co-leader of the study from the Department of Chemistry at the Imperial College London, said: “Progress in the field of early cardiovascular disease has been rather limited and slow-paced but this new probe, and others that we are developing, will go a long way to addressing this by providing real-time and easily measured responses to diagnostic enzymes.”
Dr Joe Boyle, the other co-leader of the study from the National Lung and Heart Institute, commented: “Ultimately, these probes could provide the basis for diagnostic tests at the GP, ambulances or in hospitals for quick identification of cardiovascular diseases. The probes could also provide real-time analysis of the underpinning biological processes involved in vascular disease, providing new insights and potentially new ways to track the progress of chronic disease.”
How does the new probe work?
The enzyme emitted during IPHs is called heme oxygenase-1 (HO-1), an enzyme that previous detection methods have failed in providing accurate real-time changes – a problem that the new design has solved. The chemical probe is comprised of two components capable of hosting fluorescent (glowing) molecules; one of the components is the donor, which transfers the glowing molecules to the acceptor component. Contact with HO-1 causes the bond between the components to break, resulting in a build-up of glowing molecules in the donor component.
This accumulation increases the fluorescent intensity of the probe, which can be identified through the method of spectroscopy, with the team reporting a six-fold increase of the fluorescence of the probe in tests utilising modified E. coli cells containing human HO-1.
Professor James Leiper, the associate medical director at the BHF, said: “Current methods to detect IPH rely on hospital-based imaging techniques that are both times consuming and expensive. The current technology aims to produce a fast and sensitive diagnostic test that can be used at the time that a patient first presents with symptoms to allow early detection of IPH. Use of such a test would allow for more rapid treatment and improved outcomes for patients suffering from IPH.”
The team have recently attained patents for their probe and are continuing their studies with mammal and human cells.