Integrating the Totality of Food and Nutrition Evidence for Public Health Decision Making and Communication

The interpretation and integration of epidemiological studies detecting weak associations (RR < 2) with data from other study designs (e.g., animal models and human intervention trials) is both challenging and vital for making science-based dietary recommendations in the nutrition and food safety communities. The 2008 ILSI North America “Decision-Making for Recommendations and Communication Based on Totality of Food-Related Research” workshop provided an overview of epidemiological methods, and case-study examples of how weak associations have been incorporated into decision making for nutritional recommendations. Based on the workshop presentations and dialogue among the participants, three clear strategies were provided for the use of weak associations in informing nutritional recommendations for optimal health. First, enable more effective integration of data from all sources through the use of genetic and nutritional biomarkers; second, minimize the risk of bias and confounding through the adoption of rigorous quality-control standards, greater emphasis on the replication of study results, and better integration of results from independent studies, perhaps using adaptive study designs and Bayesian meta-analysis methods; and third, emphasize more effective and truthful communication to the public about the evolving understanding of the often complex relationship between nutrition, lifestyle, and optimal health

Macrophages, lipid metabolism and gene expression in atherogenesis: a therapeutic target of the future?

Cardiovascular disease results in more deaths globally than any other ailment. A major contributing factor to its pathology is atherosclerosis; an inflammatory disorder characterized by the development of fibrotic plaques within the arterial walls. Key to the progression of atherosclerosis are macrophages that contribute to plaque development by transforming into lipid-loaded foam cells upon internalization of modified lipoproteins. Accumulation of such foam cells in the arterial wall initiates the formation of fatty streaks that subsequently develop into advanced plaques that are prone to rupture. Clearly, macrophage lipid metabolism and foam cell biology represent a key avenue of research during the ongoing search for novel therapeutic targets that can be used in the clinical intervention of atherosclerosis. In this article, we aim to summarize the current status of research on macrophages, lipid metabolism and gene expression in relation to atherogenesis and both current and potential future therapies

Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque.

The cellular composition of human atherosclerotic plaques was analyzed by immunologic techniques. Plaques were removed from the internal carotid artery during surgery, and a panel of monoclonal antibodies was used to identify cell types. Macrophages stained by Anti-Leu-M3 were found throughout the plaque, particularly in the lipid core region, where 60% of the cells reacted with this antibody. T cells expressing the T3 antigen were most abundant in the fibrous cap, where they constituted 20% of the cell population. T cells were also isolated from the plaque and detected by a rosetting test; many of these T cells were activated, as indicated by the expression of HLA-DR. Other types of leukocytes were uncommon in the plaque. An antibody to the intermediate filament protein, desmin, was used as a marker for smooth muscle cells since some, but not all, vascular smooth muscle cells contain this protein. The desmin-positive cells were uncommon in the nonatherosclerotic intima but were more numerous in the plaque. In conclusion, atherosclerotic plaques are heterogeneous with respect to cellular composition. The smooth muscle cell dominates in the fibrous cap, which also contains many T cells; the lipid core is dominated by macrophages. We suggest that interactions between smooth muscle cells and blood-borne cells are important in the pathogenesis of atherosclerosis