Role of Low‐Density Lipoprotein in Early Vascular Aging Associated With Systemic Lupus Erythematosus

Abstract

Objective. Patients with systemic lupus erythematosus (SLE) often have atherosclerotic complications at a young age but normal low-density lipoprotein (LDL) levels. This study was undertaken to investigate the role of LDL composition in promoting early vascular aging in SLE patients.Methods. Plasma LDL from 45 SLE patients (SLE-LDL) and from 37 normal healthy controls (N-LDL) was chromatographically divided into 5 subfractions (L1-L5), and the subfraction composition was analyzed. Correlations between subfraction levels and signs of early vascular aging were assessed. Mechanisms of lipid-mediated endothelial dysfunction were explored using in vitro assays and experiments in apoE −/− mice.Results. The L5 percentage was increased 3.4 times in the plasma of SLE patients compared with normal controls. This increased percentage of SLE-L5 was positively correlated with the mean blood pressure (r = 0.27, P = 0.04), carotid intima-media thickness (IMT) (right carotid IMT, r = 0.4, P = 0.004; left carotid IMT, r = 0.36, P = 0.01), pulse wave velocity (r = 0.29, P = 0.04), and blood levels of CD16+ monocytes (r = 0.35, P = 0.004) and CX3CL1 cytokines (r = 0.43, P < 0.001) in SLE patients. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis revealed that plasma levels of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF) were increased in SLE-LDL and in the SLE-L5 plasma subfraction. Injecting SLE-LDL, SLE-L5, or LPC into young, male apoE −/− mice caused increases in plasma CX3CL1 levels, aortic fatty-streak areas, aortic vascular aging, and macrophage infiltration into the aortic wall, whereas injection of N-LDL or SLE-L1 had negligible effects (n = 3-8 mice per group). In vitro, SLE-L5 lipid extracts induced increases in CX3CR1 and CD16 expression in human monocytes; synthetic PAF and LPC had similar effects. Furthermore, lipid extracts of SLE-LDL and SLE-L5 induced the expression of CX3CL1 and enhanced monocyte-endothelial cell adhesion in assays with bovine aortic endothelial cells.Conclusion. An increase in plasma L5 levels, not total LDL concentration, may promote early vascular aging in SLE patients, leading to premature atherosclerosis.

The role of postprandial very-low-density lipoprotein in the development of atrial remodeling in metabolic syndrome

“…With a multistep linear gradient of buffer B (1 M NaCl in buffer A) at a flow rate of 2 mL/min under observation at 280 nm, the LDL-χ and VLDL-χ subfractions were eluted, separately concentrated by using Centriprep filters (YM-30; EMD Millipore Corp., Billerica, MA) and sterilized by being passed through 0.22-μm filters. The protein concentration of the LDL and VLDL samples was measured by using the Lowry method [ 31 , 32 ].…”

Association of Electronegative LDL with Macrophage Foam Cell Formation and CD11c Expression in Rheumatoid Arthritis Patients

“…L5 also upregulates the expression of IL-6 and IL-8 on both monocytes and macrophages. We have previously shown that L5 induces the expression of lectin-like oxidized LDL receptor-1 (LOX-1) [15], a receptor that is involved in a variety of atherogenic responses including foam cell formation [16]. The combination of foam cell accumulation and increased cytokine activity in the microenvironment synergistically promotes plaque formation (Figure 4).…”

“…Increasing evidence indicates a vital role for L5 in the pathogenesis of atherosclerosis [14]. We recently reported that an elevated the percentage of L5 in LDL (L5%) is associated with an increased CVD risk in patients with RA or systemic lupus erythematosus [15,16]. Therefore, it is important to study the role of L5 in foam cell formation in macrophages.…”

The Role of Postprandial Very-Low-Density Lipoprotein ­in the Development of Atrial Remodeling in Metabolic Syndrome

“…With a multistep linear gradient of buffer B (1 M NaCl in buffer A) at a ow rate of 2 mL/min under observation at 280 nm, the LDL-χ and VLDL-χ subfractions were eluted, separately concentrated by using Centriprep lters (YM-30; EMD Millipore Corp., Billerica, MA) and sterilized by being passed through 0.22-μm lters. The protein concentration of the LDL and VLDL samples was measured by using the Lowry method [31,32].…”