Implicancias en el desarrollo de aterosclerosis de los niveles de expresión del receptor de alfa 2 macroglobulina, LRP1, en monocitos de sangre periférica

CHIABRANDO GA

Virtual

Congreso; Cuarta Reunión Conjunta de Sociedades de Biología de la República Argentina; 2020

XXXVII Annual Scientific Meeting of the Tucumán Biology Association XXIII Annual Scientific Meeting of the Córdoba Biology Society XXXVIII Annual Scientific Meeting of the Cuyo Biology Society Argentine Biology Society Rosario Biology Society Chilean Soci

ALPHA-2 MACROGLOBULIN RECEPTOR/LRP1 EXPRESSION IN PERIPHERAL BLOOD MONOCYTES: IMPLICATIONS IN THE ATHEROSCLEROSISChiabrando GACentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. E-mail: gustavo.chiabrando@unc.edu.arAtherosclerosis is a chronic inflammatory process of the arterial wall. In general, the evolution of this disease occurs as a subclinical form (SCAT) and is characterized by early endothelial dysfunction, dyslipidemia, arterial hypertension, and sub-endothelial accumulation of low-density lipoproteins. Endothelial dysfunction also facilitates adhesion and extravasation of peripheral blood monocytes (PBMo), which at the level of the vascular intima undergo differentiation processes to macrophages and foam cells that exacerbate the inflammatory condition and atheroma formation. The alpha-2 macroglulin receptor/LRP1 (for Low-density lipoprotein Receptor-related Protein 1), through cellular processes of endocytosis and intracellular signaling, mediates various events of cell adhesion, migration, proliferation and differentiation, remodeling of the extracellular matrix and control of the pro-inflammatory response. LRP1 is expressed in macrophages and vascular smooth muscle cells where it plays a key role in atheroma formation. Although LRP1 is also expressed in PBMo, its functional relationship with the development of SCAT is unknown. Through an observational clinical study, the expression of LRP1 in PBMo subpopulations (classical/CD14++CD16−, intermediate/CD14++CD16+ and nonclassical/CD14+CD16++) was analyzed (N = 227; 20-59 years) in individuals enrolled under informed consent at the Hospital Privado Universitario de Córdoba (CRI-HP 4-178). Through anthropometric, biochemical, and imaging data (Doppler ultrasound of Carotid and Coronary Calcium ScoreAgatston Score), three study groups were classified: low risk (LRG; N = 21; 15 males; 6 females), intermediate risk (IRG; N = 82; 29 males; 53 females) and ATSC (SCATG; N = 124; 46 males; 78 females). By flow cytometry measured LRP1, CD36, CD11b and CD11c in different PBMo subpopulations. LRP1 showed a very significant decrease in total (P = 0.0004) and classical (P = 0.0002) PBMo and a moderate decrease in intermediate (P = 0.0083) and non-classical (P = 0.0206) PBMo in individuals with SCAT compared to the other study groups. No significant changes in the other monocyte markers were observed between the study groups. By quantitative PCR, a decreased level of mRNA for LRP1 was established in classical PBMo in the SCATG compared to the other groups (P = 0.0002). In these individuals a significant increase in mRNA levels for IL-1β (P = 0.0014), TNF-α (P = 0.0121), CCL2 (P = 0.0069) and CCR2 (P = 0.0429) were found in classical PBMo. In conclusion, the expression of LRP1 in association with the pro-inflammatory profile of classical PBMo constitutes a potential diagnostic tool for atherosclerosis.