LDL subfraction linked to vascular ageing and heart disease in SLE

Patients with systemic lupus erythematosus (SLE) have signs of early vascular ageing and an increased risk of cardiovascular disease, but do not have increased concentrations of low-density lipoprotein (LDL) in their blood compared with healthy individuals. LDL can be separated into five increasingly electronegative subfractions (L1–L5), of which L5 is known to be atherogenic. For the first time, researchers have examined the L5 subfraction from patients with SLE and investigated its role in SLE-associated cardiovascular changes.

Credit: MEHAU KULYK/Science Photo Library

In the new study, patients with SLE had less total plasma LDL than healthy individuals but a higher percentage of the L5 subfraction, which correlated with clinical measures of vascular ageing. The researchers tested the atherogenic properties of LDL from patients with SLE by injecting it into Apoe^–/– mice. These atherosclerosis-prone mice developed signs of vascular ageing and atherosclerosis in response to LDL from patients with SLE, but not in response to LDL from healthy individuals.

“We found a high content of lysophosphatidylcholine and platelet-activating factor in the total LDL preparations from patients with SLE, especially in the L5 subfractions,” say corresponding authors Liang-Yin Ke, Jeng-Hsien Yen and Chu-Huang Chen. “These inflammatory mediators can lead to the differentiation of monocytes into pro-inflammatory CD16⁺ cells.”

CD16⁺ monocytes were present at increased numbers in the blood of patients with SLE compared with healthy individuals. Interestingly, both plasma concentrations of the chemokine CX₃CL1 and expression of its receptor CX₃CR1 on CD16⁺ monocytes were also increased in patients with SLE compared with healthy individuals.

patients with SLE had less total plasma LDL than healthy individuals but a higher percentage of the L5 subfraction

“Through CX₃CL1–CX₃CR1 interactions, CD16⁺ monocytes adhere to the damaged endothelium, which facilitates their penetration into the subendothelium,” explains first author Hua-Chen Chan. “This cascade of events, induced by L5 LDL, contributes to endothelial dysfunction and vascular ageing, thereby providing a novel explanation for the early onset of atherosclerosis-associated complications in patients with SLE,” she concludes.