The results could lead to better treatment for cardiovascular disease – the second leading cause of death in Canada.
Glycomics researchers at the University of Alberta and CHU Sainte-Justine are reporting a discovery that could lead to new therapies for cardiovascular disease.
Researchers have identified a new mechanism responsible for plaque buildup on artery walls, a process known as atherosclerosis. This plaque, made up of fat, cholesterol, and other substances, can restrict blood flow and is a major factor in cardiovascular disease.
“We have identified a new mechanism that underlies atherosclerosis,” said Chris Cairo, a professor in the department of chemistry and co-lead author of the new study. We have also shown that this can be treated pharmacologically. Using inhibitors developed in our laboratory, we have found that these could be a novel strategy for therapies in cardiovascular disease. “
The discovery has set drug targets that have the power to stop plaque buildup – a breakthrough that could make a big difference for many Canadians. Canada’s second leading cause of death, cardiovascular disease affects 2.4 million people nationwide, according to the federal government. And Cairo explained that there is still a need for new and more effective treatments.
“The clinical implications of this study include discovering a new pathway that contributes to atherosclerosis – one of the main causes of cardiovascular mortality – and setting new targets that can be used in treatment that can prevent atherosclerosis independently of cholesterol levels,” said co-lead author Alexey Pshezhetsky of CHU Sainte-Justine.
The researchers examined the role of glycosylation of lipid molecules circulating in the blood in atherosclerosis. Low-density lipoproteins (LDL), sometimes called bad cholesterol, are a group of fats, cholesterol, and glycoproteins. Researchers studied LDL particles before and after removing a specific residue from glycans, known as sialic acid. LDL that had sialic acids removed was more absorbed by cells than those that were not modified. Animal models deficient in enzymes that remove sialic acids have less formation of atherosclerotic plaque, indicating that these enzymes could be new targets for future therapy.
“The work is built on several years of basic research, and we hope it leads to benefits for clinical treatment,” said Cairo, who indicated that the study was conducted on animal models and would require more preclinical research before applying it to human clinical trials.
Cairo and Pshezhetsky are both network investigators with GlycoNet, a pan-Canadian networking center of excellence with more than 170 researchers in the field of glycomics, centered at A.
This research was funded by GlycoNet and conducted in collaboration with a postdoctoral fellow, Tianlin Guo, and graduate student, Radhika Chakraberty, who works at U of A.
“It was exciting to see that this project goes to the next stage, which is one step closer to clinical implementation,” said Warren Wakarchuk, professor in the Department of Biological Sciences and Scientific Director of GlycoNet. “As a leader in glycomics research, GlycoNet is proud to support the development of health innovations that improve the quality of life of patients and their families in Canada and around the world.”
The study, “Neuraminidases 1 and 3 for atherosclerosis by removing low-density lipoproteins and increasing their absorption by macrophages”, is published in Journal of the American Heart Association.