Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: Possible contribution of phospholipase A2 to this atherogenic profile

Autor: Javier Pedreño, Silvia Paredes, Germán Camejo, Eva Hurt-Camejo, Lluís Masana, Pere Benito, Joan-Carles Vallvé, Birgitta Rosengren, Peter Sartipy, Olov Wiklund
Rok vydání: 2001
Předmět:
Zdroj: Arthritis & Rheumatism. 44:2761-2767
ISSN: 1529-0131
0004-3591
DOI: 10.1002/1529-0131(200112)44:12<2761::aid-art463>3.0.co;2-5
Popis: Objective. This work studied the presence of inflammatory and atherogenic lipoprotein markers that could explain the high incidence of cardiovascular disease (CVD) reported in rheumatoid arthritis (RA) patients. Methods. Inflammatory markers were 1) soluble adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C-reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon-y [IFNy], tumor necrosis factor a [TNFa]), and 5) secretory group IIA phospholipase A 2 (sPLA 2 -IIA). Atherogenic lipoprotein markers were 1) the size distribution of plasma lipoprotein subclasses, and 2) the binding affinity of low-density lipoprotein (LDL) to chondroitin 6-sulfate glycosaminoglycan (GAG). Results. RA patients (n = 31) and matched controls (n = 28) had similar plasma concentrations of total cholesterol, triglycerides, Apo B, Apo A-I, very low-density lipoprotein, intermediate-density lipoprotein, and high-density lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA 2 -IIA, ICAM, CRP, Fb, TNFa, and IFNy compared with controls. RA patients also had significantly higher levels of small, dense LDL-1 (P < 0.05) and lower levels of small HDL-2 particles (P < 0.001) compared with controls. In addition, LDL from RA patients had a significantly higher binding affinity (K d ) to GAG (mean ± SD K d 204 ± 22.4 nM Apo B) than did LDL from control subjects (K d 312 ± 36 nM Apo B) (P < 0.05). This K d value showed a significant negative correlation with the plasma levels of LDL-1 (r = -0.566, P ≤ 0.004). In RA patients, a significant positive correlation was obtained between sPLA 2 -IIA and CRP, ICAM, and LDL-1. HDL-2 showed a negative correlation with sPLA 2 -IIA. Conclusion. These atherogenic lipoprotein factors combined with the presence of chronic inflammation may contribute to the high CVD-related mortality in RA patients.
Databáze: OpenAIRE
Externí odkaz: