Molecules., 2021., 24(8): pii, E1509.

The influence of diet on microRNAs that impact cardiovascular disease.

Kura, B Parikh, M Slezak, J Pierce, G.N.

Abstract

Food quality and nutritional habits strongly influence human health status. Extensive research has been conducted to confirm that foods rich in biologically active nutrients have a positive impact on the onset and development of different pathological processes, including cardiovascular diseases. However, the underlying mechanisms by which dietary compounds regulate cardiovascular function have not yet been fully clarified. A growing number of studies confirm that bioactive food components modulate various signaling pathways which are involved in heart physiology and pathology. Recent evidence indicates that microRNAs (miRNAs), small single-stranded RNA chains with a powerful ability to influence protein expression in the whole organism, have a significant role in the regulation of cardiovascular-related pathways. This review summarizes recent studies dealing with the impact of some biologically active nutrients like polyunsaturated fatty acids (PUFAs), vitamins E and D, dietary fiber, or selenium on the expression of many miRNAs, which are connected with cardiovascular diseases. Current research indicates that the expression levels of many cardiovascular-related miRNAs like miRNA-21, -30 family, -34, -155, or -199 can be altered by foods and dietary supplements in various animal and human disease models. Understanding the dietary modulation of miRNAs represents, therefore, an important field for further research. The acquired knowledge may be used in personalized nutritional prevention of cardiovascular disease or the treatment of cardiovascular disorders.

Key Points

MicroRNAs (miRNAs) are short RNA sequences belonging to the non-coding region of RNA. They have significant effect on the expression of a wide range of proteins that will ultimately affect different molecular pathways. Significant differences have been observed in the expression of many miRNAs in various diseases compared to healthy subjects.  The main goal of this review is to summarize recent information and studies concerned with the beneficial effects of bioactive dietary compounds on the cardiovascular system, with particular attention on the expression of different miRNAs. Understanding the mechanisms of action of nutrients through modulation of miRNA expression could be helpful in the prevention or treatment of diseases connected with the cardiovascular system. Among cardioprotective nutritional components that can effect the expression of miRNAs are omega-3 and omega-6 PUFAs. PUFAs downregulate miRNA-146a in endothelial cells with lipopolysaccharide-induced inflammation.

Omega-3 PUFAs were able to reverse an angiotensin II-induced increase of miRNA-21 expression in mouse cardiac fibroblasts, therefore, they may exert potential beneficial effects in cardiac fibrosis. miRNA-21 is also connected with CVD and inflammation. Diets with a high content of PUFAs downregulate miRNA-21, which reduces pro-inflammatory signaling. Omega-3 PUFAs regulate miRNA-19b, -146b and -183 in Wistar rats. Administration of omega-3 PUFAs upregulated levels of these miRNAs and suppressed inflammatory markers compared with non-treated rats.

Bioactive dietary components like PUFAs, vitamins, and minerals can be effective in CVD prevention and treatment due to their ability to change miRNAs expression, thereby modulating important pathways involved in lipid metabolism, endothelial function, hypertrophy and/or fibrosis. The capacity of food nutrients to modulate miRNAs involved in heart function and development (mainly miRNA-1, -21, -133 and -155) gives further rationale for the need for additional research to determine if these interactions between food and miRNAs can serve as viable targets for novel therapeutic approaches to CVD.