Electronegative LDL Is Associated with Plaque Vulnerability in Patients with Ischemic Stroke and Carotid Atherosclerosis

Puig N, Camps-Renom P, Solé A et al. Antioxidants (Basel). 2023 Feb 10;12(2):438. doi: 10.3390/antiox12020438. PMID: 36829998


Abstract: Owing to the high risk of recurrence, identifying indicators of carotid plaque vulnerability in atherothrombotic ischemic stroke is essential. In this study, we aimed to identify modified LDLs and antioxidant enzymes associated with plaque vulnerability in plasma from patients with a recent ischemic stroke and carotid atherosclerosis. Patients underwent an ultrasound, a CT-angiography, and an 18F-FDG PET. A blood sample was obtained from patients (n = 64, 57.8% with stenosis ≥50%) and healthy controls (n = 24). Compared to the controls, patients showed lower levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apoB), apoA-I, apoA-II, and apoE, and higher levels of apoJ. Patients showed lower platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON-1) enzymatic activities in HDL, and higher plasma levels of oxidized LDL (oxLDL) and electronegative LDL (LDL(−)). The only difference between patients with stenosis ≥50% and <50% was the proportion of LDL(−). In a multivariable logistic regression analysis, the levels of LDL(−), but not of oxLDL, were independently associated with the degree of carotid stenosis (OR: 5.40, CI: 1.15–25.44, p < 0.033), the presence of hypoechoic plaque (OR: 7.52, CI: 1.26–44.83, p < 0.027), and of diffuse neovessels (OR: 10.77, CI: 1.21–95.93, p < 0.033), indicating that an increased proportion of LDL(−) is associated with vulnerable atherosclerotic plaque.

Funding: This research was funded by grants 201716.10 from Fundació La Marató TV3, PID 2020-113634RB-C22 from Ministerio de Ciencia e Innovación, and FIS PI19/00421 and PI20/00334 from the Instituto de Salud Carlos III (co-financed by the European Regional Development Fund). N.P. is funded by the Instituto de Salud Carlos III predoctoral contract FI20/00252. S.B. and JLSQ. are members of CIBER of Diabetes and Metabolic Diseases (CIBERDEM, CB07/08/0016, Instituto de Salud Carlos III Project). S.B., P.C.-R., J.M.-F. and A.A.-S. are members of RICORS-ICTUS (RD21/0006/0006). S.B., J.L.S.-Q., and N.P. are members of the Quality Research Group 2017-SGR– 1149 from Generalitat de Catalunya, and of the Spanish Atherosclerosis Society Vascular Biology Group. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU) is accredited by CERCA Programme/Generalitat de Catalunya.