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

Molecular Mechanism for Changes in Proteoglycan Binding on Compositional Changes of the Core and the Surface of Low-Density Lipoprotein–Containing Human Apolipoprotein B100

“…These results are in agreement with data of Grass et al 23 and with results from patients with rheumatoid arthritis who have increased plasma levels of sPLA 2 . 13 Taken together, our results are consistent with the hypothesis that sPLA 2 modification of LDL in the circulation leads to exposure of site A, resulting in increased proteoglycan binding. Furthermore, the conformational change of apoB in sPLA 2 -modified LDL is caused by the formation of smaller LDL and by changes in the phospholipid composition of the LDL particle.…”

“…8 Thus, clarification of the proatherogenic mechanisms by which sPLA 2 acts in the plasma and in the artery wall is important to our understanding of the pathogenesis of the disease. To investigate the molecular mechanism for how circulating sPLA 2 induces the increased binding affinities of LDL to glycosaminoglycans, 13 we crossed our human apoB transgenic mice with mice expressing sPLA 2 . 23 The serum activity of sPLA 2 in these transgenic mice is elevated approximately 8-fold compared with nontransgenic littermates, but there is no evidence of systemic inflammation in the transgenic mice.…”

“…Lipolysis of LDL by sPLA 2 alters the expression of apoB100 epitopes on the LDL particle, 11 and sPLA 2 -modified LDL display increased interaction with glycosaminoglycans. 12 The plasma concentration of sPLA 2 is increased in systemic inflammations, such as rheumatoid arthritis (RA), 13 which is known to be associated with increased risk of coronary heart disease, and LDL from RA patients has increased binding affinities to glycosaminoglycans. 13 Willner et al recently showed that the enrichment of cholesterol of LDL is another important risk factor for atherosclerosis; triglyceride-rich apoB-containing lipoproteins are not as atherogenic as those containing cholesteryl esters.…”

“…12 The plasma concentration of sPLA 2 is increased in systemic inflammations, such as rheumatoid arthritis (RA), 13 which is known to be associated with increased risk of coronary heart disease, and LDL from RA patients has increased binding affinities to glycosaminoglycans. 13 Willner et al recently showed that the enrichment of cholesterol of LDL is another important risk factor for atherosclerosis; triglyceride-rich apoB-containing lipoproteins are not as atherogenic as those containing cholesteryl esters. 14 The authors proposed that the inflammatory response in atherosclerosis occurs primarily in response to toxicity from cholesterol accumulation in lesions.…”

Serum Lipid Alterations in Early Rheumatoid Arthritis Patients on Disease Modifying Anti Rheumatoid Therapy

“…They have also shown reduced levels of albumin in these patients which perhaps indicate a reduced rate of synthesis of proteins by the liver reflected in the decreased levels of the apoproteins [15]. Study by Eva Hurt Camejo et al [16] showed an Apo B decrease by 7 %, while Apo A-I, TC, TG, IDL and HDL were in the normal range in the RA patients and similar to those in the controls.…”