LRP1 EXPRESSION IS DOWNREGULATED IN HUMAN AND MOUSE MONOCYTE SUBPOPULATIONS DURING ATHEROSCLEROTIC PROCESSES

ALBERTINI R; FERRER D; AMIGONE JL; COLLINO CJ; TINTI M; CAPRA RH; CASTRO C; CHIABRANDO GA

Amsterdam

Simposio; ISA 2015. 7th International Symposium on Atherosclerosis; 2015

IAS: International Atherosclerosis Society

LRP1 EXPRESSION IS DOWNREGULATED IN HUMAN AND MOUSE MONOCYTE SUBPOPULATIONS DURING ATHEROSCLEROTIC PROCESSESAbstract nr. 643Author Chiabrando , Gustavo, Facultad de Ciencias Quimicas Universidad Nacional de Cordoba, Cordoba, ArgentinaCo-author(s) - Albertini , RicardoCo-author(s) - Ferrer , DarioCo-author(s) - Amigone , JoseCo-author(s) - Collino , CesarCo-author(s) - Tinti , MariaCo-author(s) - Capra , RaulCo-author(s) - Castro , ClaudiaTopic The Pathogenesis of Atherosclerosis; Immunity, Inflammation, and the Endothelium Keywords Animal model,Atherosclerosis,Immunity,InflammationAtherosclerosis is an inflammatory process in which circulating monocytes are involved. Three monocyte subpopulations (MoSP) are characterized in human: classical, intermediate and nonclassical, whereas murine MoSP are basically LyC6hi and LyC6lo. The low-density lipoprotein receptor-related protein 1 (LRP1) is expressed in several tissues, included monocytes. LRP1 is involved in vascular remodeling and foam cell formation. However, LRP1 expression in MoSP in atherosclerosis is unclear. Herein we determine LRP1 levels in MoSP in patients with atherosclerotic lesions and in a murine model of atherosclerosis (apolipoprotein E deficient mice:KO-ApoE-/-) by flow cytometry (FC). Peripheral blood samples were obtained from: i) healthy individuals (HI group) (cholesterol<200mg/dl; HDL-cholesterol>40mg/dl (male); >50mg/dl (female), triglycerides<150mg/dl, creatinin<1,2 mg/dl, arterial pressure<140/90, without antecedents of arterial hypertension, nonsmoking, and without familiar antecedents of CVD; ii) patients (AP group) with evident atherosclerotic plaques or thickening of the vascular intima in carotid (>1.0 mm) (carotid Doppler ultrasound study) and/or coronary artery calcium (CAC) score >1 (computed tomography scanning); and iii) patients (nonAP group) excluded of HI group without carotid and coronary atherosclerotic lesions. Characteristics of patient groups are shown in Table 1. Peripheral blood samples from KO-ApoE-/- mice (12 weeks of age) maintained with low-fat diet (LFD) or high-fat diet (HFD) for 4 weeks were analyzed. Under these food conditions only HFD mice developed atherosclerotic plaques. Human MoSP were selected by FC strategy using specific fluorochrome-conjugated antibodies (F-MoAb) against CD45/LRP1/CD14/CD161. Murine Ly-C6 MoSP were selected using F-MoAb against monocytic markers (CD11b/Ly-6G/Ly-6C/LRP1. The inclusion of LRP1 as fourth marker identified three murine MoSP: Ly-6Chi/LRP1hi, Ly-6Chi /LRP1lo, and Ly-6Clo/LRP1lo (Table 2). The mean fluorescence intensity (MFI) for LRP1 in each MoSP was determined from CD14/CD16 (human)1 and Ly-6C/LRP1 plots (mouse). MFI-LRP1 values calculated are shown in Table 2. Human LRP1 was significantly decreased in classicalmonocytes in AP group in comparison to HI and nonAP groups. Mouse LRP1 was significantly decreased in Ly-6ChiLRP1hi MoSP in KO-ApoE-/- HFD with respect to LFD mice. Thus, LRP1 expression in MoSP constitutes an attractive diagnostic tool for subjects with high risk of cardiovascular disease.1 Ferrer D. et al., Cytometry Part A. 2014, 85, 601-610. Funding supports: PICTO-GSK-2012-0084; PICT-2012-2607.