Houston Methodist researchers have found that sure elements of so-called “good” ldl cholesterol — high-density lipoproteins (HDL) – could also be related to an elevated prevalence of heart problems.
Led by Henry J. Pownall, Ph.D., professor of biochemistry in drugs on the Houston Methodist Analysis Institute, and Khurram Nasir, M.D., M.P.H., a heart specialist and division chief of cardiovascular prevention and wellness at Houston Methodist, the analysis group is utilizing modern strategies to research the position of sure properties of HDL in coronary heart well being.
“Throughout routine checkups, adults have their levels of cholesterol examined, which incorporates each ‘unhealthy’ (LDL) and ‘good’ (HDL) ldl cholesterol,” mentioned Pownall, who’s the corresponding writer on a examine that appeared within the Journal of Lipid Analysis, a month-to-month peer-reviewed scientific journal established in 1959 and revealed by the American Society for Biochemistry and Molecular Biology. “Not all ldl cholesterol, nonetheless, is born the identical. What is just not generally acknowledged is that every sort of ldl cholesterol has two varieties – free ldl cholesterol, which is energetic and concerned in mobile capabilities, and esterified, or certain, ldl cholesterol, which is extra steady and able to be saved within the physique. An excessive amount of free ldl cholesterol, even whether it is in HDL, might contribute to coronary heart illness.”
In pre-clinical research, the analysis group found that HDL with a excessive content material of free ldl cholesterol is probably going dysfunctional. To validate their findings and show their speculation, they’re at the moment on the midway level of the NIH-funded Houston Coronary heart Examine wherein they are going to be finding out 400 sufferers with a spread of plasma HDL concentrations. Pownall and Nasir are the co-PIs of the examine.
Essentially the most shocking discovering from our examine to date is that there’s a sturdy hyperlink between the quantity of free ldl cholesterol in HDL and the way a lot of it accumulates in white blood cells known as macrophages, which may contribute to coronary heart illness,”
Henry J. Pownall, Ph.D., professor of biochemistry in drugs on the Houston Methodist Analysis Institute
Whereas it was beforehand thought that the switch of free ldl cholesterol to HDL was useful for coronary heart well being by eradicating extra ldl cholesterol from tissues, Pownall mentioned their knowledge reveals that within the context of excessive plasma HDL concentrations, the reverse is true, whereby free ldl cholesterol switch from HDL to the white blood cells in blood and tissues might really increase one’s danger for heart problems.
The researchers say as soon as they attain their rapid aim of displaying that extra free ldl cholesterol in HDL is related to extra heart problems, they plan to develop new diagnostics and coverings for managing coronary heart illness, in addition to use HDL-free ldl cholesterol as a biomarker to establish sufferers requiring HDL-lowering therapies.
“We anticipate with the ability to attain our first aim in lower than three years, as there are some identified medicine that have an effect on free ldl cholesterol in pre-clinical fashions, so this might be examined in people if our checks justify using these identified therapeutics,” Pownall mentioned.
If they’re profitable, Pownall proposes that they might doubtlessly have the ability to apply what they be taught to sufferers in a medical setting as shortly as six years from now.
Pownall and Nasir’s collaborators on this examine had been Baiba Gillard, Corina Rosales, Dedipya Yelamanchili and Antonio M. Gotto Jr. with the Houston Methodist Analysis Institute; Miguel Caínzos Achirica with the Hospital del Mar Analysis Institute in Barcelona, Spain; and Alan T. Remaley with the Lipoprotein Metabolism Laboratory within the Translational Vascular Drugs Department of the Nationwide Coronary heart, Lung, and Blood Institute on the Nationwide Institutes of Well being (NIH).
This work was supported by grants from the NIH’s Nationwide Coronary heart, Lung, and Blood Institute (R01HL149804 and R01HL163535) and by the Houston Methodist Hospital Basis.
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Journal reference:
Yelamanchili, D., et al. (2025). HDL-free ldl cholesterol inflow into macrophages and switch to LDL correlate with HDL-free ldl cholesterol content material. Journal of Lipid Analysis. doi.org/10.1016/j.jlr.2024.100707.
