Fatty material is stickier than LDL, making it more likely to attach to artery walls
SCIENTISTS from the University of Warwick in the UK have discovered a new form of ‘ultra-bad’ cholesterol that increases the risk of heart disease. The fatty material is stickier than the common form of ‘bad’ cholesterol, making it more likely to attach to artery walls.
Funded by the British Heart Foundation (BHF), the researchers found that ‘ultra-bad’ cholesterol, called MGmin-low-density lipoprotein (LDL), which is more common in people with type 2 diabetes and the elderly, appears to be ‘stickier’ than normal LDL. This makes it more likely to attach to the walls of arteries. When LDL attaches to artery walls it helps form the dangerous ‘fatty’ plaques’ that cause coronary heart disease (CHD).
The research – published online on May 26 in the journal Diabetes – shows how the make-up and the shape of a type of LDL cholesterol found in diabetics could make it more harmful than other types of LDL. The findings provide one possible explanation for the increased risk of coronary heart disease in people with diabetes. Understanding exactly how ‘ultra-bad’ LDL damages arteries is crucial, as this knowledge could help develop new anti-cholesterol treatments for patients.
The researchers made the discovery by creating human MGmin-LDL in the laboratory, then studying its characteristics and interactions with other important molecules in the body. They found that MGmin-LDL is created by the addition of sugar groups to ‘normal’ LDL – a process called glycation – making LDL smaller and denser.
By changing its shape, the sugar groups expose new regions on the surface of the LDL. These exposed regions are more likely to stick to artery walls, helping to build fatty plaques. As fatty plaques grow they narrow arteries – reducing blood flow – and they can eventually rupture, triggering a blood clot that causes a heart attack or stroke.
The discovery might also explain why metformin, a widely prescribed type 2 diabetes drug, seems to lead to reduced heart disease risk. Metformin is known to lower blood sugar levels, and this new research shows it may reduce the risk of CHD by blocking the transformation of normal LDL to the more ‘sticky’ MGmin-LDL.
Dr Naila Rabbani, Associate Professor of Experimental Systems Biology at Warwick Medical School, who led the study, said: “We’re excited to see our research leading to a greater understanding of this type of cholesterol, which seems to contribute to heart disease in diabetics and elderly people. Type 2 diabetes is a big issue…particularly common in lower income groups and South Asian communities. The next challenge is to tackle this more dangerous type of cholesterol with treatments that could help neutralize its harmful effects on patients’ arteries.”
Dr Shannon Amoils, Research Advisor at the BHF, said: “We’ve known for a long time that people with diabetes are at greater risk of heart attack and stroke. There is still more work to be done to untangle why this is the case, but this study is an important step in the right direction.”
U.S. Halts ‘Good Cholesterol’ Study
Meanwhile, U.S. officials abruptly halted a major study Wednesday of a drug that boosts people’s good cholesterol did not go on to prevent heart attacks or strokes.
The disappointing findings involve super-strength niacin (Niaspan), a type of B vitamin that many doctors already prescribe as potential heart protection. The failed study marks the latest setback in the quest to harness good cholesterol to fight the bad kind.
The trial, called AIM-HIGH, looked at whether adding Niaspan — a high-dose, extended-release form of niacin, or vitamin B3 — to certain heart-disease patients’ statin drug regimens would prevent more cardiac events than a statin alone.
“This sends us a bit back to the drawing board,” said Dr Susan Shurin, cardiovascular chief at the National Institutes of Health. The study tested Abbott Laboratories’ Niaspan, an extended-release form of niacin that is a far higher dose than is found in dietary supplements. As expected, the Niaspan users saw their beneficial HDL levels rise and their levels of risky triglycerides drop more than people who took a statin alone.
But the combination treatment did not reduce heart attacks, strokes, or the need for artery-clearing procedures such as angioplasty, the NIH said. It led the NIH to stop the study 18 months ahead of schedule.