Common antidepressants might help liver cells clear a dangerous type of cholesterol
Common antidepressants might offer an unexpected benefit by helping liver cells absorb and clear a stubborn, disease-causing type of cholesterol. This cellular discovery could eventually lead to dual-purpose treatments for patients facing both depression and cardiovascular risks.
Recent research published in the Journal of Lipid Research suggests that certain antidepressants could help liver cells more effectively absorb lipoprotein(a), a type of cholesterol linked to increased risk of heart disease. Lipoprotein(a) is similar to low-density lipoprotein (LDL), but carries an extra protein that makes it more likely to cause artery blockages.
While traditional cholesterol-lowering medications like statins do not target this specific particle, the study indicates that some antidepressants may offer a dual benefit for patients dealing with both depression and high lipoprotein(a) levels.
The researchers from the University of Otago and the University of New South Wales conducted experiments using normal human liver cells in a lab setting. They tested the effects of imipramine, an older tricyclic antidepressant, and newer selective serotonin reuptake inhibitors (SSRIs) like citalopram, sertraline, and fluoxetine.
Imipramine unexpectedly increased the absorption of lipoprotein(a) by nearly three times compared to untreated cells. Citalopram had a similar effect, while sertraline and fluoxetine did not alter the absorption levels.
Further investigation revealed that imipramine and citalopram increased the amount of lipoprotein(a) anchored to the cell surface, which is a necessary step for cellular absorption. The drugs also boosted the receptor that captures lipoprotein(a) molecules on the cell surface. However, sertraline did not enhance absorption, likely because it interferes with a protein called dynamin, which is required for the process.
Serotonin, a chemical messenger increased by these antidepressants, appeared to be the key driver of the surface binding. Adding pure serotonin to the cell cultures produced the same effects as the drugs. This suggests that by raising serotonin levels outside the cells, the antidepressants make the liver cells more receptive to absorbing lipoprotein(a).
The findings offer a potential new treatment avenue for patients at risk of heart disease due to high levels of lipoprotein(a). The study highlights the importance of understanding how specific antidepressants interact with lipid metabolism, potentially leading to more targeted therapies for conditions affecting both mental health and cardiovascular health.
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