High-density lipoprotein (HDL), or 'good' cholesterol, normally protects against heart and artery disease by helping to keep blood vessels clear, researchers said.
Now, researchers at Cleveland Clinic, US, have found the process by which HDL becomes dysfunctional, loses its cardio-protective properties and instead promotes inflammation and atherosclerosis, or the clogging and hardening of the arteries.
The beneficial and cardio-protective properties of HDL have been studied and reported extensively, yet all clinical trials of pharmaceuticals designed to raise HDL levels have so far failed to show that they significantly improve cardiovascular health, researchers said.
This disconnect, as well as recent research showing that a protein abundant in HDL is present in an oxidised form in diseased artery walls, spurred the research team - led by Stanley Hazen, Vice Chair of Translational Research for the Lerner Research Institute - to study the process by which HDL becomes dysfunctional.
Apolipoprotein A1 (apoA1) is the primary protein present in HDL, providing the structure of the molecule that allows it to transfer cholesterol out of the artery wall and deliver it to the liver, from which cholesterol is excreted.
It's apoA1 that normally gives HDL its cardio-protective qualities, but Hazen and his colleagues have discovered that in the artery wall during atherosclerosis, a large proportion of apoA1 becomes oxidised and no longer contributes to cardiovascular health, but rather, contributes to the development of coronary artery disease.
Over the course of more than five years, Hazen and his colleagues developed a method for identifying dysfunctional apoA1/HDL and discovered the process by which it is oxidised and turned dysfunctional in the artery wall.
They then tested the blood of 627 cardiology patients for the dysfunctional HDL and found that higher levels raised the patient's risk for cardiovascular disease.
"Identifying the structure of dysfunctional apoA1 and the process by which it becomes disease-promoting instead of disease-preventing is the first step in creating new tests and treatments for cardiovascular disease," said Hazen.
The study was published in the journal Nature Medicine.