Researchers have found that certain elements of “good” cholesterol, known as high-density lipoproteins (HDL), might be linked to a higher occurrence of cardiovascular disease.
Researchers have identified that specific components of “good” cholesterol, which is referred to as high-density lipoproteins (HDL), could be related to a greater risk of cardiovascular disease.
The study was led by Henry J. Pownall, Ph.D., who is a biochemistry professor at the Houston Methodist Research Institute, along with Khurram Nasir, M.D., M.P.H., a cardiologist and head of cardiovascular prevention and wellness at Houston Methodist. Their research team is employing innovative techniques to explore how certain characteristics of HDL impact heart health.
Pownall, the lead author of the study published in the Journal of Lipid Research, explained, “During regular medical checkups, adults typically get their cholesterol levels measured, including both ‘bad’ cholesterol (LDL) and ‘good’ cholesterol (HDL). However, it’s not widely understood that there are two forms of cholesterol: free cholesterol, which is active and has a role in cellular functions, and esterified cholesterol, which is more stable and can be stored in the body. An excess of free cholesterol, even when it’s part of HDL, may contribute to heart disease.”
In early studies, the research team found that HDL that contains a lot of free cholesterol tends to be dysfunctional. To test their theory, they are currently halfway through the NIH-funded Houston Heart Study, examining 400 patients with different levels of plasma HDL. Pownall and Nasir are co-principal investigators on this research.
Pownall noted, “The most surprising result from our ongoing study has been the significant correlation between the amount of free cholesterol present in HDL and the extent to which it builds up in macrophages, a type of white blood cell that can contribute to heart disease.”
Previously, it was believed that transferring free cholesterol to HDL was beneficial for heart health by helping to eliminate excess cholesterol from cells. However, Pownall states that their findings suggest that in cases of high plasma HDL concentrations, the opposite could be true, as free cholesterol moving from HDL to white blood cells in blood and tissues might increase the risk of cardiovascular disease.
The researchers aim to demonstrate that excess free cholesterol in HDL correlates with heightened cardiovascular disease risk, and they plan to create new diagnostics and therapies for heart disease management. They also aim to utilize HDL-free cholesterol as a marker to identify patients who might need treatments to reduce HDL levels.
Pownall expressed optimism about reaching their initial goal within three years, noting that some established drugs have shown effects on free cholesterol in pre-clinical studies, making human testing feasible if their results support the use of these therapies.
If their efforts succeed, Pownall anticipates that the insights gained could be translated into clinical applications for patients within six years.
Collaborating with Pownall and Nasir on this study were researchers Baiba Gillard, Corina Rosales, Dedipya Yelamanchili, and Antonio M. Gotto Jr. from the Houston Methodist Research Institute, as well as Miguel Caínzos Achirica from the Hospital del Mar Research Institute in Barcelona, Spain, and Alan T. Remaley from the Lipoprotein Metabolism Laboratory at the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH).
This research was supported by grants from the NIH’s National Heart, Lung, and Blood Institute (R01HL149804 and R01HL163535) and the Houston Methodist Hospital Foundation.
