Autoimmune Rheumatic Diseases: An Update on the Role of Atherogenic Electronegative LDL and Potential Therapeutic Strategies
Por:
Chen, DY, Sawamura, T, Dixon, RAF, Sanchez-Quesada, JL, Chen, CH
Publicada:
1 may 2021
Resumen:
Atherosclerosis has been linked with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Autoimmune rheumatic diseases (AIRDs) are associated with accelerated atherosclerosis and ASCVD. However, the mechanisms underlying the high ASCVD burden in patients with AIRDs cannot be explained only by conventional risk factors despite disease-specific factors and chronic inflammation. Nevertheless, the normal levels of plasma low-density lipoprotein (LDL) cholesterol observed in most patients with AIRDs do not exclude the possibility of increased LDL atherogenicity. By using anion-exchange chromatography, human LDL can be divided into five increasingly electronegative subfractions, L1 to L5, or into electropositive and electronegative counterparts, LDL (+) and LDL (-). Electronegative L5 and LDL (-) have similar chemical compositions and can induce adverse inflammatory reactions in vascular cells. Notably, the percentage of L5 or LDL (-) in total LDL is increased in normolipidemic patients with AIRDs. Electronegative L5 and LDL (-) are not recognized by the normal LDL receptor but instead signal through the lectin-like oxidized LDL receptor 1 (LOX-1) to activate inflammasomes involving interleukin 1 beta (IL-1 beta). Here, we describe the detailed mechanisms of AIRD-related ASCVD mediated by L5 or LDL (-) and discuss the potential targeting of LOX-1 or IL-1 beta signaling as new therapeutic modalities for these diseases.
Filiaciones:
Chen, DY:
China Med Univ Hosp, Rheumatol & Immunol Ctr, Taichung 404, Taiwan
China Med Univ, Coll Med, Taichung 404, Taiwan
China Med Univ Hosp, Translat Med Ctr, Taichung 404, Taiwan
Sawamura, T:
Shinshu Univ, Sch Med, Dept Mol Pathophysiol, Matsumoto, Nagano 3908621, Japan
Shinshu Univ, Inst Biomed Sci, Dept Life Innovat, Matsumoto, Nagano 3908621, Japan
Dixon, RAF:
Texas Heart Inst, Mol Cardiol Res Labs, Houston, TX 77030 USA
Sanchez-Quesada, JL:
CIBER Diabet & Metab Dis CIBERDEM, Barcelona 08041, Spain
Biomed Res Inst IIB St Pau, Cardiovasc Biochem Grp, Barcelona 08041, Spain
Chen, CH:
Texas Heart Inst, Vasc & Med Res, Houston, TX 77030 USA
Shinshu Univ, Inst Biomed Sci, Dept Life Innovat, Matsumoto, Nagano 3908621, Japan
New York Heart Res Fdn, Mineola, NY 11501 USA
gold, Green Published
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