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An international collaboration jointly led by University College Dublin (UCD) and the Monash University of Melbourne has shown that imitating the activity of naturally occurring molecules in the body could constitute a new approach to the treatment of vascular diseases related to diabetes.
Diabetes is a huge challenge for global health. Currently, 425 million people suffer from diabetes and this figure is expected to reach 750 million by 2025. It is estimated that 10% of our national health budget is related to the management of diabetes and related complications.
People with diabetes have a high incidence of cardiovascular disease. An accumulation of fat and immune cells [plaque] on the blood vessels causes inflammation and plaque development. If a plaque breaks, it can clog a blood vessel and deprive the brain of oxygen, resulting in a stroke.
In healthy conditions, the body produces special messenger molecules that tightly control inflammation. In diseases such as diabetes, the inflammation can become so strong that it unnecessarily disrupts the activity of these messengers and these rages.
This study led by Dr. Eoin Brennan of the UCD and researchers in Melbourne as part of an EU-funded project took a radical approach of mimicking the activity of these messengers using a synthetic version of a molecule called lipoxin.
"I first worked with colleagues at the UCD School of Chemistry headed by Professor Patrick Guiry to design a synthetic version of lipoxin called Benzo-LXA4." Then I went to the lab. from Professor Mark Cooper and Dr. Phillip Kantharidis in Melbourne to examine the potential of using natural lipoxin and this synthetic mimic in the treatment of vascular complications in diabetic animals, and we were pleased to see that not only was this diminishing the amount of plaque in the blood vessels but that it was reversing established heart disease, "says Dr. Brennan.
Dr. Brennan returned to the UCD for the next phase of the project, which involved treating human carotid plaque tissue with these protective molecules to determine if the results obtained in the laboratory were also clinically relevant. To do this, Ms. Mary Barry and a team of vascular surgeons from St. Vincent's University Hospital in Dublin provided carotid plaque biopsy tissue after surgery to allow UCD researchers to test the effects of lipoxin-based drugs on the patient's tissues.
By taking tissue from the plaque in human blood vessels and exposing it to lipoxin molecules in the laboratory, the research team found that inflammation was reduced. These findings provide insights into the process of vascular involvement seen in atherosclerosis, particularly in the context of diabetes, and to identify lipoxins as a new drug for diabetes complications.
Importantly, the team has shown that lipoxins can prevent the progression of atherosclerosis in animals with established atherosclerotic lesions. The study builds on earlier work by these scientists who have shown that these compounds reverse established diabetic nephropathy.
Catherine Godson, co-lead author and director of the UCD Research Center on Complications of Diabetes and a member of the UCD Conway Institute, said: "This study highlights the protective lipoxins of complications The problems with anti-inflammatories are well documented .
Here we used an alternative approach, softer and softer than just blocking inflammation. Instead, we favored its resolution by imitating the processes that keep us healthy. Based on these findings, we recently received international support from the Juvenile Diabetes Research Foundation to examine how these lipoxin molecules interact with existing diabetes therapies. "
Professor Mark Cooper, Head of the Department of Diabetes at the Monash University Central Clinic and a global researcher in the field of diabetes and its complications, said: "In itself, this international collaboration is an example bringing together chemists from synthesis, biomedical researchers and clinicians to transfer the results of laboratory models to ex vivo tissue samples from patients. "
The research is published in the current issue of the journal Diabetes.
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More information:
E. P. Brennan et al. Lipoxins protect against inflammation in atherosclerosis associated with diabetes, Diabetes (2018). DOI: 10.2337 / db17-1317
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