Kyung-Hyun Cho, Jae-Yong Kim, Eun-Young Lee and Ki-Hoon Park
School of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea
It has been well established that pro-inflammatory HDL is a biomarker for atherosclerosis in patients with rheumatoid arthritis (RA). Although oxidized LDL is a traditional biomarker of atherosclerosis, there has been many reports that it is also found in RA patients, suggesting lipoprotein metabolism is important in the pathogenesis of RA. In order to investigate a physiological role of lipoprotein in RA. We analyzed serum lipoproteins from rheumatoid arthritis (RA) both male and female patients. Although they showed normal level of TC, LDL-C, and glucose level RA group showed significant elevation of serum TC, uric acid, CETP activity. LDL in RA group was more oxidized and glycated with more fragmentation of apo-B, suggesting more severe oxidative damage, especially in female group. The LDL was more easily uptaken into macrophage via phagocytosis with more production of oxidized species. HDL from RA group was also showed more glycated and aggregation of apoA-I. With increase of CETP activity and TG contents in lipoproteins, paraoxonase activity was reduced in HDL of RA group. RA group showed elevation of advanced glycated end (AGE) product and severe multimerization of apoA-I in HDL. Microinjection of LDL caused severe death of zebrafish embryo in RA group. Under presence of oxidized LDL, HDL3 from RA group lost protectional activity from embryo death around 2-fold higher mortality than control. In conclusion, RA patients showed severely altered lipoprotein profile with dysfunctional HDL, which are very similar properties with that of coronary heart patients.
Keywords: Rheumatoid arthritis, lipoproteins, cardiovascular disease, glycation.