Association of cholesterol efflux capacity with plasmalogen levels of high-density lipoprotein: A cross-sectional study in chronic kidney disease patients

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Maeba R, Kojima K, Nagura M, Komori A, Nishimukai M, Okazaki T, and Uchida S. (2018). Association of cholesterol efflux capacity with plasmalogen levels of high-density lipoprotein: A cross-sectional study in chronic kidney disease patients. Atherosclerosis, 270: 102-109

Atherosclerosis is an arterial disease characterized by fats deposited along the inner walls of arteries. This disease can cause pain, fatigue, and muscle weakness localized to the area of the body experiencing reduced circulation due to a blockage. If this blockage reduces blood circulation to the brain the person may also experience confusion. Chronic kidney disease (CKD), the gradual loss of kidney function, will accelerate the progression of atherosclerosis and can also increase the risk for cardiovascular disease. People with CKD can also experience hypertension, diabetes mellitus, anemia, hypoproteinemia, and reduced lipid levels. Overtime CKD can lead to end-stage renal disease (ESRD), the advanced stage of kidney disease, and potential complete failure of the organ. Maeba et al analyzed blood samples from 24 mild to moderate CKD (CKD-3-4) and 33 ESRD (CKD-5) patients to study the plasmalogen levels within plasma and within high density lipoprotein (HDL) particles, the ability of HDL to accept cholesterol from macrophages, and whether phospholipid treatment can improve cholesterol transport.

Within both patient groups two classes of plasmalogens, ethanolamine plasmalogens (PlsEtn) and choline plasmalogens (PlsCho) in plasma and HDL were analyzed.  All were found to be significantly decreased in the CKD-5 group compared to the CKD-3-4 group indicating further disease progression. It is interesting to note that although plasmalogens were decreased in the plasma (PlsEtn decreased from 66.6 ± 28.9 µM to 38.8 ± 13.4 µM, P < 0.0001 and PlsCho decreased from 54.5 ± 16.8 µM to 39.8 ± 15.2 µM, P = 0.002), the greatest difference in plasmalogen levels were seen in the HDL particle fraction from the CKD-5 patients (PlsEtn decreased from 55.5 ± 8.2 µM to 28.1 ± 18.0 µM, P < 0.0001 and PlsCho decreased from 37.0 ± 11.4 µM to 22.9 ± 10.5 µM, P = 0.0004). No difference in plasmalogen levels were detected within erythrocytes.

To determine the cholesterol efflux capacity of HDL, macrophages labelled with [3H]-cholesterol were grown and the percentage of total radioactive cholesterol released into growth medium was calculated. The CKD-5 patients had decreased cholesterol efflux capacity compared to the CKD-3-4 group (8.6 ± 3.1 compared to 13.6 ± 3.7), further supporting the advanced prognosis of the CKD-5 group and suggesting that the inability to remove cholesterol from macrophages occurs at later stages of the disease. To study this association further, a number of phospholipid species, including PlsEtn or PlsCho, were added to re-constituted HDL or ERSD HDL to determine if the cholesterol efflux capacity could be improved with the treatment. Compared with all other phospholipid species tested, PlsEtn and PlsCho treatments showed the greatest improvement with a 1.4-fold increase in efflux capacity of the re-constituted HDL and nearly 2-fold in the ESRD-HDL.

Maeba et al demonstrated the association and potential role that plasmalogens have within CKD and atherosclerosis, and the differences found throughout the progression of the disease. The reduction in HDL plasmalogens in CKD-5 patients was associated with the reduction in cholesterol efflux capacity of HDL. In addition, supplementing with plasmalogens resulted in an increased cholesterol efflux capacity of HDL, indicating that plasmalogen level is a significant factor in the transport of cholesterol. Further it was demonstrated that providing plasmalogens was able to recover the atheroprotective effect of HDL. Impaired cholesterol transport has been associated with other diseases, including Alzheimer’s disease and other dementias. Future studies evaluating the cholesterol efflux of HDL in patients with dementias supplemented with plasmalogens is certainly warranted to evaluate whether there could be a therapeutic benefit.