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Cardiovascular diseases (CVDs) rank as the first leading cause of death globally. High dietary polyphenol (especially flavonoids) intake has strongly been associated with low incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. Phytogenic flavonoids affect the physiological and pathological processes of CVDs by modulating various biochemical signaling pathways. Non-coding RNAs (ncRNAs) have attracted increasing attention as fundamental regulator of gene expression involved in CVDs. Among the different ncRNA subgroups, long ncRNAs (lncRNAs) have recently emerged as regulatory eukaryotic transcripts and therapeutic targets with important and diverse functions in health and diseases. lncRNAs may be associated with the initiation, development and progression of CVDs by modulating acute and chronic inflammation, adipogenesis and lipid metabolism, and cellular physiology. This review summarizes this research on the modulatory effects of lncRNAs and their roles in mediating cellular processes. The mechanisms of action of flavonoids underlying their therapeutic effects on CVDs are also discussed. Based on our review, flavonoids might facilitate a significant epigenetic modification as part (if not full) of their tissue-/cell-related biological effects. This finding may be attributed to their interaction with cellular signaling pathways involved in chronic diseases. Certain lncRNAs might be the target of specific flavonoids, and some critical signaling processes involved in the intervention of CVDs might mediate the therapeutic roles of flavonoids.

Epigenetic mechanisms underlying the benefits of flavonoids in cardiovascular health and diseases: are long non-coding RNAs rising stars?