Nutrients and Gene Expression in Cardiovascular Disease

The pathogenesis of atherosclerosis features a complex interplay of genetic and environmental factors, among which are specific nutrient intakes and nutrient combinations in diets. A large number of in vitro and in vivo studies have consistently found that specific unsaturated FAs and polyphenols affect the expression levels of genes related to the cardiovascular systems in a protective fashion, thus contributing to explaining benefits associated with diets and foods rich in these components. The possibility of reducing major cardiovascular events by administering a monoclonal antibody against IL-1b in a trial (CANTOS) of secondary CVD prevention (Ridker et al., 2017) shows that vascular inflammation is a true viable target to reduce the burden of CVD. The greatest challenge is now to interfere with vascular inflammatory pathways physiologically, exploiting natural strategies without appreciable side effects. These have the potential to tackle the roots of vascular disease before the occurrence of its clinical manifestations (i.e., in primary cardiovascular prevention). The road ahead is indicated by the scientific evidence reviewed earlier, linking the intake of natural compounds, through mechanisms being unraveled in molecular detail, with favorable outcomes. The use of global transcriptional profiling is a powerful tool in current nutrigenomic studies. This allows dynamic changes in gene expression to be measured before and after adding a nutrient or a nutrient metabolite in cultured endothelial cells, monocytes and macrophages, and SMCs, all of which are relevant for atherosclerosis. This highlights novel nutrientresponsive genes and detailing associated plausible nodes of signaling pathways. To date, most in vivo human nutrigenomic studies have used PBMCs as a feasible cell type for gene expression studies. However, nutrigenomic effects can be tissue-dependent and gene expression measurements in human tissues other than PBMCs, such as adipose tissue cells, have been increasingly considered. An important challenge for cardiovascular nutrigenomic studies in humans is to correlate tissue-specific transcriptomic signatures with proteomic, metabolomic, and microbiome data and with systemic effects. Integration of different "omics" techniques and the classical biomarkers with nutritional information using a systems biology approach is instrumental to achieving a comprehensive view of the biological response to nutrients to be exploited for preventing and treating CVD. Furthermore, more attention is warranted to examine the variability in cell or tissue response to such nutrients, examining gene expression profiles in responders versus nonresponders, because vascular healthful effects of specific nutrients and nutrient combinations may depend on inherited genetic variants affecting their uptake, metabolism, and responses. Probing this complexity will lead to a more global understanding of the influence of environmental and genetic factors conditioning the specific response to nutrients.