Enzyme modified non-oxidative LDL (ELDL) is effectively taken up by vascular smooth muscle cells (SMC) and mediates transition into foam cells and produces phenotypic changes in SMC function. Our data show that incubation of human coronary artery SMC (HCASMC) with low concentration of ELDL (10 μg/ml) results in significantly enhanced foam cell formation compared to oxidized LDL (200 μg/ml; p < 0.01) or native LDL (200 μg/ml; p < 0.01). Bioinformatic network analysis identified activation of p38 MAPK, NFkB, ERK as top canonical pathways relevant for biological processes linked to cell migration and osteoblastic differentiation in ELDL-treated cells. Functional studies confirmed increased migration of HCASMC upon stimulation with ELDL (10 μg/ml) or Angiopoietin like protein 4, (ANGPTL4, 5 μg/ml), and gain in osteoblastic gene profile with significant increase in mRNA levels for DMP-1, ALPL, RUNX2, OPN/SPP1, osterix/SP7, BMP and reduction in mRNA for MGP and ENPP1. Enhanced calcification of HCASMC by ELDL was demonstrated by Alizarin Red staining. In summary, ELDL is highly potent in inducing foam cells in HCASMC and mediates a phenotypic switch with enhanced migration and osteoblastic gene profile. These results point to the potential of ELDL to induce migratory and osteoblastic effects in human smooth muscle cells with potential implications for migration and calcification of SMCs in human atherosclerosis.

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Hospital survival associated with the use of thromboprophylaxis in patients with severe COVID-19 infection Survival and thromboprophylaxis in COVID-19 Abstract Introduction: It has been described that patients with severe or critical infection by COVID-19 suffer an inflammatory state that conditions a high thrombotic risk. However, there is little information on how to address thrombotic risk, coagulopathy, and anticoagulant therapy in these patients. Objective: To evaluate the use of thromboprophylaxis in patients with severe COVID-19 infection associated with longer survival. Material and methods: Retrospective cohort study, in a 2nd level hospital. 340 records of patients hospitalized for severe COVID-19 infection were reviewed, and 171 were included in the final analysis. Sociodemographic data, previous pathologies, days of hospital stay, respiratory parameters were evaluated; blood gas, hematic cytometry, DHL, C-reactive protein (CRP), antiviral treatment, thromboprophylaxis, use of steroids and use of antibiotics, the study variable was survival associated with the use of LMWH. Descriptive, inferential statistics, univariate and multiple models were used. Results: Advanced age, PaO2 / FiO2 index> 200 and high CRP were associated with a higher probability of death. And the greater the number of days of use of thromboprophylaxis; the higher the degree of protection. The PaO2 / FiO2 index> 200 (adjusted HR 0.270; 95%CI;. 0.100-0.727) and greater number of days with thromboprophylaxis (adjusted HR, 0.576; 95%CI;. 0.460 – 0.721) during hospitalization, were factors associated with hospital survival. Conclusions: In this study we found evidence to recommend the use of thromboprophylaxis from the first hours of admission in adult patients with severe COVID-19 as long as there are no contraindications for it, due to the increase in hospital survival. KEY WORDS: Thromboprophylaxis, LMWH, SARS-CoV-2, survival, Severe COVID-19 infection.