Effects of mycophenolate mofetil on key pattern of coronary restenosis: a cascade of in vitro and ex vivo models

BACKGROUND: Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is a rationally designed immunosuppressive drug. The current study investigates the effect of MMF on key pattern of restenosis in a cascade of in vitro and ex vivo models. METHODS: Part I of the study investigated in northern blot and cytoflow studies the effect of MMF (50, 100, 150, 200, 250, and 300 μg/mL) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1) in human coronary endothelial cells (HCAEC) and human coronary medial smooth muscle cells (HCMSMC). Part II of the study applied a human coronary 3D model of leukocyte attack, the 3DLA-model. HCAEC and HCMSMC were cultured on both sides of a polycarbonate filters, mimicking the internal elastic membrane. Leukocyte attack (LA) was carried out by adding human monocytes (MC) on the endothelial side. The effect of MMF (50 μg/mL) on adhesion and chemotaxis (0.5, 1, 2, 3, 4, 6, and 24 h after LA) and the effect on proliferation of co-cultured HCMSMC (24 h after LA) was studied. In part III of the study a porcine coronary organ culture model of restenosis (POC-model) was used. After ex vivo ballooning MMF (50 μg/mL) was added to the cultures for a period of 1, 2, 3, 4, 5, 6, and 7 days. The effect on reactive cell proliferation and neointimal thickening was studied at day 7 and day 28 after ballooning. RESULTS: Expression of ICAM-1 in northern blot and cytoflow studies was neither clearly inhibited nor stimulated after administration of MMF in the clinical relevant concentration of 50 μg/mL. In the 3DLA-model 50 μg/mL of MMF caused a significant antiproliferative effect (p < 0.001) in co-cultured HCMSMC but had no effect on MC-adhesion and MC-chemotaxis. In the ex vivo POC-model neighter reactive cell proliferation at day 7 nor neointimal hyperplasia at day 28 were significantly inhibited by MMF (50 μg/mL). CONCLUSION: Thus, the data demonstrate a significant antiproliferative effect of clinical relevant levels of MMF (50 μg/mL) in the 3DLA-model. The antiproliferative effect was a direct antiproliferative effect that was not triggered via reduced expression of ICAM-1 or via an inhibition of MC-adhesion and chemotaxis. Probably due to technical limitations (as e.g. the missing of perfusion) the antiproliferative effect of MMF (50 μg/mL) could not be reproduced in the coronary organ culture model. A cascade of focused in vitro and ex vivo models may help to gather informations on drug effects before large experimental studies are initiated

Characterisation of health literacy strengths and weaknesses among people at metabolic and cardiovascular risk: Validity testing of the Health Literacy Questionnaire

Objectives: Health literacy refers to the ability of individuals to gain access to, use, and understand health information and services in order to maintain a good health. The assessment of health literacy profiles in a population is potentially crucial to respond to health needs. The Health Literacy Questionnaire explores nine dimensions of health literacy and has been shown to display robust psychometric properties. The aim was to test the validity of the multidimensional Health Literacy Questionnaire and to describe the health literacy profiles in a French population at risk of cardiovascular disease. Methods: Data were collected using self-administered questionnaires from 175 participants attending health education and support programmes in local associations of patients in Paris. Analysis included scale reliability, confirmatory factor analysis, and health literacy profiles via descriptive statistics. Results: In confirmatory factor analysis, the nine-factor structure was close to the original Health Literacy Questionnaire. A nine-factor confirmatory factor analysis model was fitted to the 44 items with no cross-loadings or correlated residuals allowed. Given the restricted nature of the model, the fit was satisfactory: χ 2 WLSMV (866 df) = 1383.81, p = 0.0000, comparative fit index = 0.925, Tucker–Lewis index = 0.918, root mean square error of approximation = 0.058, weighted root mean square residual = 1.175. Composite reliability ranged from 0.77 to 0.91. Among the 9 scales of the Health Literacy Questionnaire, the highest scores were found for scale 1 ‘Feeling understood and supported by healthcare professionals’ and scale 9 ‘Understand health information enough to know what to do’ and the lowest for scale 2 ‘Having sufficient information to manage my health’ and scale 7 ‘Navigating the healthcare system’. Conclusion: The French version of the Health Literacy Questionnaire was shown to be psychometrically robust with good reliability. In the context of France, the 9 scales of Health Literacy Questionnaire allow a thorough assessment of health literacy strengths and weaknesses to respond to health literacy needs and improve the accessibility of health information and services