Autoimmune rheumatic diseases : An update on the role of atherogenic electronegative ldl and potential therapeutic strategies
Chen, D.Y. (College of Medicine. China Medical University)
Sawamura, T. (Department of Life Innovation. Institute for Biomedical Sciences. Shinshu University)
Dixon, R.A.F. (Molecular Cardiology Research Laboratories. Texas Heart Institute)
Sanchez-Quesada, Jose Luis (Institut d'Investigació Biomèdica Sant Pau)
Chen, C.H. (New York Heart Research Foundation)

Date:	2021
Abstract:	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 composi-tions 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 1β (IL-1β). 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-1β signaling as new therapeutic modalities for these diseases.
Note:	Altres ajuts: Vascular and Medicinal Research Fund, Texas Heart Institute (#765-64050), Houston, TX, USA; Ministry of Science and Technology (Taiwana grant MOST 107-2314-B-039-053-MY3); Ministerio de Sanidad, Spain (co-financed by Fondo Europeo de Desarrollo Regional (FEDER)).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Electronegative LDL ; L5 ; Atherosclerotic cardiovascular disease (ASCVD) ; Autoimmune rheumatic diseases (AIRDs) ; Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) ; Interleukin 1β (IL-1β)
Published in:	Journal of clinical medicine, Vol. 10 Núm. 9 (january 2021) , p. 1992, ISSN 2077-0383

DOI: 10.3390/jcm10091992
PMID: 34066436

15 p, 1.2 MB

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