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building blocks spell out 'good' and 'bad'

When So-called ‘Good’ Cholesterol Goes Bad

Cleveland Clinic researchers discover how it happens

Most of us have heard about “good” cholesterol. But this so-called “good” cholesterol can turn bad – by losing its cardio-protective properties and promoting inflammation and coronary artery disease.

Cleveland Clinic researchers have discovered the process by which high-density lipoprotein (HDL) – the carrier of so-called “good” cholesterol – becomes dysfunctional.The discovery represents the first step toward creating new tests and treatments for cardiovascular disease.

The research team was led by Stanley Hazen, MD, PhD, vice chair of translational research for the Lerner Research Institute and section head of preventive cardiology and rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic.

Scientific evidence prompts inquiry

Two pieces of evidence spurred the Cleveland Clinic research team to study the process by which HDL becomes dysfunctional:

  • The beneficial and cardio-protective properties of HDL have been studied and reported extensively. But so far, clinical trials of drugs designed to raise HDL cholesterol levels have failed to significantly improve cardiovascular health.
  • Recent research has demonstrated that the major protein in HDL is present in an oxidized form in diseased artery walls.

The story begins with apolipoprotein A1 (apoA1), the primary protein present in HDL molecules. ApoA1 provides 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.

ApoA1 normally gives HDL its cardio-protective qualities. But Dr. Hazen and his colleagues have discovered that in the artery wall during atherosclerosis, a large proportion of apoA1 becomes oxidized and no longer contributes to cardiovascular health. Instead, apoA1actually becomes pro-inflammatory and contributes to the development of coronary artery disease.

Over the course of more than five years, Dr. Hazen and his colleagues developed a method for identifying and quantifying dysfunctional apoA1/HDL. They discovered how it becomes oxidized and turns dysfunctional in the artery wall.

Then they tested the blood of 627 Cleveland Clinic cardiology patients for the dysfunctional HDL. They found that higher levels raised the patients’ risk for cardiovascular disease.

First step toward improved assessment and therapies

“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,” Dr. Hazen says.

“Once we learned what dysfunctional HDL looked like, we were able to develop a clinical test to measure its levels in the bloodstream,” he says. “This will be a valuable tool for assessing patients’ cardiovascular disease risk and for guiding development of HDL-targeted therapies to prevent or reverse heart disease.”

The research also points toward new therapeutic targets for pharmaceuticals, such as those designed to prevent the formation of dysfunctional HDL and the development or progression of atherosclerosis.

The research was published online Sunday in the journal Nature Medicine.

More information

Tags: bad cholesterol, cholesterol, coronary artery disease, good cholesterol, innovation, research
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  • GeorgeBMac

    Congratulations to Dr Hazen and the Cleveland Clinic for yet another ground breaking revelation in the quest to prevent heart disease…