Discovery May Break Down Cholesterol Mystery

Dr. Spencer Proctor says chylomicrons gather on arterial walls and may as dangerous or more dangerous than low-density lipoprotein (LDL) cholesterol in causing strokes and heart attacks.

"We were the first in the world to label chylomicrons remnants with florescence and visually show that these particles can accumulate in arterial vessels," Proctor said. "Our next goal is to figure out why they get stuck and whether or not they play a significant role in the development of coronary artery disease – our suspicion now is that they do."

Chylomicrons are metabolized balls of fat and cholesterol that enter your blood stream through your intestines after a meal – usually within about 15 minutes after your last bite. However, because chylomicrons are processed so quickly, when a patient gives a blood sample after fasting for 12 hours or more, as per doctors' usual orders, chylomicron cholesterol will usually comprise just three per cent of all the cholesterol in the sample.

LDL cholesterol is the most prevalent type of cholesterol, usually comprising about 70 per cent of all cholesterols found in blood samples taken from patients who have fasted for 12 hours or more. For this reason, most researchers believe LDL cholesterol, which is produced in the liver and delivered to the rest of the body over a period of days after food is ingested, is the leading culprit among cholesterols in the development of coronary artery disease.

However, researchers have also been at a loss to explain why 40 per cent of people who are highly vulnerable to suffering a stroke or heart attack have low or normal LDL levels.

"That's why we believe chylomicrons and their remnants are the key to solving this problem," said Proctor, whose research is published in the November issue of Arteriosclerosis, Thrombosis and Vascular Biology. "We believe understanding chylomicrons and their metabolism may answer all questions about cholesterol and the role it plays in the development of diabetes, obesity, and other cardiovascular diseases."

Researchers have known about chylomicrons for decades, but it took Proctor's initial research with his colleagues in Australia to discover how they are broken down after a meal. Using unique and specially designed imaging tools, Proctor and his colleagues tracked the formation and delivery pathways of chylomicrons in rabbits. Their research showed that chylomicron remnants form smaller lipoproteins, which can build up more quickly in arteries than any other type of cholesterol-carriers, including LDL.

"At the moment, not enough is known about chylomicron remnants and their pathways," Proctor said. "As a first goal, I'd like to see a greater awareness among clinicians about the significance of chylomicrons to cardiovascular disease and how to test their metabolism in humans."

"We know that you don't need to have raised concentrations of LDL to have high levels of chylomicrons," he added. "And it may well be that chylomicrons could be a significant risk factor for developing heart disease and stroke."

Proctor arrived at the U of A as a visiting researcher two years ago on loan from Curtin University in Perth, Australia, thanks to a grant from the National Health and Medical Research Council of Australia. He has since become a faculty professor. His research is attracting the attention of pharmaceutical companies interested in funding his future work in this area.

An internationally celebrated scholar, Proctor has already received funding from National Heart Foundation of Australia, the Juvenile Diabetes Research Foundation and the Japanese Atherosclerosis Society. Last month at the Canadian Lipoprotein Conference, Proctor received the Pfizer Young Investigator Award, which comes with a $25,000 research prize.