Soluble low-density lipoprotein receptor-related protein 1 as a surrogate marker of carotid plaque inflammation assessed by 18F-FDG PET in patients with a recent ischemic stroke

Garcia E, Camps-Renom P, Puig N et al. J Transl Med. 2023 Feb 19;21(1):131. doi: 10.1186/s12967-022-03867-w. PMID: 36805772

Background 18F-fuorodeoxyglucose positron emission tomography (18F-FDG PET) identifes carotid plaque infam‑ mation and predicts stroke recurrence. Aim Our aim was to evaluate the performance of soluble low-density lipoprotein receptor-related protein 1 (sLRP1) as an indicator of carotid plaque infammation.
Methods A prospective study was conducted among adult patients with recent (<7 days) anterior circulation ischemic stroke and at least one atherosclerotic plaque in the ipsilateral internal carotid artery. Patients under‑ went an early (<15 days from inclusion) 18F-FDG PET, and the maximum standardized uptake value (SUVmax) within the plaque was measured. sLRP1 levels were measured in plasma samples by ELISA. The association of sLRP1 with SUVmax was assessed using bivariate and multivariable linear regression analyses. Hazard ratios (HR) were esti‑ mated with Cox regression to evaluate the association between circulating sLRP1 and stroke recurrence.
Results The study was conducted with 64 participants, of which 57.8% had ≥50% carotid stenosis. The multivari‑ able linear and logistic regression analyses showed that sLRP1 was independently associated with (i) SUVmax within the plaque (β=0.159, 95% CI 0.062–0.257, p=0.002) and (ii) a probability of presenting SUVmax ≥2.85 g/mL (OR=1.31, 95% CI 1.00–1.01, p=0.046), respectively. Participants with stroke recur

Funding: The economic support to develop this project was received from Fundació La Marato TV3 (201716.10), from the Instituto de Salud Carlos III (co-fnanced by the European Regional Development funds, FEDER), FIS PI15/00884 (to JM-F), FIS PI19/00421 (to PC-R and SB) and FIS PI21/01523 (to VLl-C), from Fundación BBVA Ayudas a equipos de investigación 2019 (“Translational Molecular Imaging for Detection of Cholesterol Entrapment in the Vasculature with 68 Ga-labeled LRP1-derived Peptides” to VLl-C), from Sociedad Española de Arteriosclerosis Grant 2021 (to SB), and from Acadèmia de Ciències Mèdiques de Catalunya I Balears Grant (to DV). The team is part of CIBER of Diabetes and Metabolic Diseases (CIBERDEM, CB07/08/0016 to SB and JLS-Q) and CIBER Enfermedades Cardiovasculares (CIBERCV; CB16/11/00276 to DV and VLl-C) run by the Instituto de Salud Carlos III. AB-A. (FI19/00205) and NP (FI20/00252) are predoctoral fellows granted by the Programme_Contratos predoctorales de formación de investigación en salud_ from the Instituto de Salud Carlos III (ISCIII) and co-fnanced with ERDFs. EG, AB-A and VLl-C are members of Redes de investigación (Enfermedades Metabólicas y Cáncer RED2018-102799-T), a project run by MINECO. VLl-C, AB-A and DV are members of the Quality Research Group 2017 SGR 946 and SB, NP and JLS-Q of the 2017-SGR-1149 group from the Generalitat de Catalunya. SB, PC-R, JM-F and AA-S are mem‑ bers of RICORS-ICTUS (RD21/0006/0006), and FEDER. VLL-C, EG, NP; SB and JLS-Q are members of the Spanish Atherosclerosis Society Vascular Biology Group. IR-SANTPAU is a centre of CERCA Programme/Generalitat de Catalunya.


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.