Increased arterial stiffness is a degenerative vascular process, progressing with age that leads to a reduced capability of arteries to expand and contract in response to pressure changes. This progressive degeneration mainly affects the extracellular matrix of elastic arteries and causes loss of vascular elasticity. Recent studies point to significant interference of dietary polyphenols with mechanisms involved in the pathophysiology and progression of arterial stiffness. This review summarizes data from epidemiological and interventional studies on the effect of polyphenols on vascular stiffness as an illustration of current research and addresses possible etiological factors targeted by polyphenols, including pathways of vascular functionality, oxidative status, inflammation, glycation, and autophagy. Effects can either be inflicted directly by the dietary polyphenols or indirectly by metabolites originated from the host or microbial metabolic processes. The composition of the gut microbiome, therefore, determines the resulting metabolome and, as a consequence, the observed activity. On the other hand, polyphenols also influence the intestinal microbial composition, and therefore the metabolites available for interaction with relevant targets. As such, targeting the gut microbiome is another potential treatment option for arterial stiffness.

Institute of Microbiology of the Czech Academy of Sciences Vídeňská 1083 142 20 Prague Czech Republic

Instituto de Biologia Experimental e Tecnológica Apartado 12 2780 901 Oeiras Portugal Instituto de Tecnologia Química e Biológica Universidade Nova de Lisboa Av da República 2780 157 Oeiras Portugal CEDOC NOVA Medical School Faculdade de Ciências Médicas Universidade Nova de Lisboa Campo Mártires da Pátria 130 1169 056 Lisboa Portugal

Laboratory of Natural Products and Food Research and Analysis University of Antwerp 2610 Antwerpen Belgium

Laboratory of Pharmaceutical Pharmacology Latvian Institute of Organic Synthesis LV 1006 Riga Latvia

Laboratory of Physiopharmacology University of Antwerp 2610 Antwerpen Belgium

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