HDL cholesterol can also be bad sometimes

(Last Updated On: October 14, 2022)
HDL Cholesterol can also be bad
HDL cholesterol forms plaque when the cholesterol transport system fails. Credit: sciencemag.org

Everybody knows HDL cholesterol or High-Density Lipoprotein is good for health while LDL or Low-Density Lipoprotein is bad. However, HDL is not always good for health. One recent study shows HDL can be bad for heart health. Before getting into the topic, I would like to explain what HDL and LDL are.

HDL and LDL are the lipoproteins that carry cholesterol, fatty acids, Triacylglycerols, and proteins. There are four different types of lipoproteins, High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), Very Low-Density Lipoprotein (VLDL), and Chylomicrons.

Normally, HDL particles carry cholesterol and cholesteryl esters and cholesterol from peripheral tissues to the liver for catabolism. In opposition to the function of HDL, LDL particles carry cholesterol from the liver to peripheral tissues where cholesterol is required. Therefore, people who have a higher level of HDL cholesterol are usually healthier than others.

However, this is not always true. According to a recent study published in the Journal Science, HDL can be bad for heart health. A 67-year-old woman with a significantly high level of HDL cholesterol, that supposed to be protective against heart diseases, had been found to have plaques in her arteries. This unusual case motivated a team of researchers to think about HDL in a different way. They showed how a higher level of HDL can reveal the inability of the cholesterol system to eliminate the fatty particles from circulation.

Daniel Rader from the University of Pennsylvania, who is a geneticist and lipidologist, suggested that the level of the HDL is not as important as how quickly and effectively it moves from the blood arteries to the liver for catabolism. In fact, Rader was inspired by a mouse model that was developed about 20 years ago by researcher Monty Krieger.

During the development of the mouse model, Monty deleted a gene SCARB1 that led to the production of a higher amount of HDL particles as well as severe clogging in the arteries of the model mouse. HDL particles normally carry the cholesterol from the immune cells around the lining of the arteries and deposit cholesterol in the liver to continue the cycle.

SCARB1 is the gene that produces a protein known as SR-B1. SR-B1 protein helps HDL deposit cholesterols in the liver. Since the SCARB1 gene had been deleted in the mouse model, HDL particles were unable to deposit cholesterol in the liver for catabolism. The inability to deposit cholesterol in the liver and carrying more and more cholesterols from the blood arteries made HDL particles gain in the size.

The increased size of the HDL particles creates the problem for HDL particles to get away from the blood arteries and may aid the HDL particles to get deposited on the lining of the arteries forming plaque.

Daniel and his colleagues carried out a comparative study to understand the relationship between SCARB1 gene expression and HDL in human beings rather than in mouse models. They sequenced genes in 853 people who had a very high level of HDL particles and took 1000 people as controls (with normal HDL cholesterol levels).

During the study, they found one woman out of 852 who had no copies of the SCARB1 gene while 18 people had only one functional copy of the SCARB1 gene rather than having two copies.

The woman with no copies of the SCARB1 gene was 67 years old and had more plaques on her arteries as compared to an average woman of her age. Researchers also measured her HDL cholesterol level which was 153 mg/dl, a value higher than the average value (62 mg/dl) among women of her age.

Rader along with his colleague further studies lipids and heart disease in thousands of people. They found that 284 people had only one functional copy of the SCARB1 gene. However, there was no one with both copies of SCARB1 defective like in the case of the woman mentioned above.

In this second study, these people with one copy of the functional SCARB1 gene were producing about 80 % higher amounts of HDL particles as compared to the controls and had coronary artery disease compared with the people having the traditional risk factors such as diabetes and hypertension.

Rader said that the link between HDL transport and cardiac problems is still weak because only a few people have been found with a partially functioning SCARB1 gene. He also mentioned that HDL’s behavior in a Petri dish can’t be taken as what it is doing inside our body. Jan Albert Kuivenhoven, the genetics of lipid metabolism from the University Medical Center Groningen, Netherlands said that we have no way to perform the HDL analysis that can tell us what is happening inside a person.

HLD is an extraordinary complex and it is possible that the failure of the drugs that raise HDL levels is due to the type of HDL produced. This is because doctors detected larger HDL particles than expected size after the supplement of the drugs that causes the production of the HDL particles.

In conclusion, it is time to say a high HDL level followed by a reason. “Your HDL is high because of X and it is good” and in someone else, “Your HDL is high because of Y and that’s bad”. This is because, as we saw an increase in the level of HDL cholesterol can be due to the production of HDL particles as well as due to the defective transport of the HDL particles (because of the defective SCARB1 gene).

Reference: Journal Science

Article doi: 10.1126/science.aaf4175

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