Why Good Cholesterol May Fail To Protect Against Heart Disease

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Although well associated with lowering cardiovascular disease risk high-density lipoprotein (HDL) -- known as good cholesterol -- may not always be able to protect against heart disease.

A new study has suggested that it increases the inflammatory response of certain immune cells called macrophages.

This can potentially counteract its well-established anti-inflammatory effect in various other cell types, the study said.

"Good cholesterol's functions are not as simple as initially thought, and appear to critically depend on the target tissue and cell type," said Marjo Donners of Maastricht University, the Netherlands.

"In the end, it is the balance between its pro- and anti-inflammatory effects that determines clinical outcome," Donners added.

In the study, the researchers found that HDL treatment enhanced inflammation in macrophages, in contrast to its effects in other cell types. Similarly, macrophages taken from mice with elevated HDL levels showed clear signs of inflammation.

This pro-inflammatory effect induced by HDL showed enhanced pathogen protection, the researchers said.

Lung macrophages ingested disease-causing bacteria upon exposure to HDL. On the other hand, mice with low HDL levels were impaired at clearing these bacteria from the lungs.

The results demonstrate that HDL's pro-inflammatory activity supports the proper functioning of macrophage immune responses.

According to Donners, these findings suggest that patients with persistent infections or specific immune disorders might benefit from HDL-raising therapies.

The research could also lead to the development of cell-specific therapies that exploit the benefits of HDL-targeted therapies while avoiding the side effects, the researchers noted.

The study was published in the journal Cell Metabolism.

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