Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis - Possible contribution of phospholipase A(2) to this atherogenic profile

Objective. This work studied the presence of inflammatory and atherogenic l ipoprotein 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 (intercell ular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C-reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon-g amma [IFN gamma], tumor necrosis factor alpha [TNF alpha]), and 5) secretor y group IIA phospholipase A(2) (sPLA(2)-IIA). Atherogenic lipoprotein marke rs were 1) the size distribution of plasma lipoprotein subclasses, and 2) t he binding affinity of low-density lipoprotein (LDL) to chondroitin 6-sulfa te glycosaminoglycan (GAG). Results. RA patients (n = 31) and matched controls (n = 28) had similar pla sma concentrations of total cholesterol, triglycerides, Apo B, Apo A-I, ver y low-density lipoprotein, intermediate-density lipoprotein, and high-densi ty lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA(2)-IIA, ICAM, CRP, Fb, TNF alpha, and IFN gamma compared with control s. 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 wi th controls. In addition, LDL from RA patients had a significantly higher b inding affinity (K-d) to GAG (mean +/- SD K-d 204 +/- 22.4 nM Apo B) than d id LDL from control subjects (K-d 312 +/- 36 nM Apo B) (P < 0.05). This Kd value showed a significant negative correlation with the plasma levels of L DL-1 (r = -0.566, P <less than or equal to> 0.004). In RA patients, a signi ficant positive correlation was obtained between sPLA(2)-IIA and CRF, ICAM, and LDL-I. HDL-2 showed a negative correlation with sPLA(2)-IIA. Conclusion. These atherogenic lipoprotein factors combined with the presenc e of chronic inflammation may contribute to the high CVD-related mortality in RA patients.