Tuscany Sangiovese grape juice imparts cardioprotection by regulating gene expression of cardioprotective C-type natriuretic peptide.

Abstract

A regular intake of red grape juice has cardioprotective properties, but its role on the modulation of natriuretic peptides (NPs), in particular of C-type NP (CNP), has not yet been proven. The aims were to evaluate: (1) in vivo the effects of long-term intake of Tuscany Sangiovese grape juice (SGJ) on the NPs system in a mouse model of myocardial infarction (MI); (2) in vitro the response to SGJ small RNAs of murine MCEC-1 under physiological and ischemic condition; (3) the activation of CNP/NPR-B/NPR-C in healthy human subjects after 7days' SGJ regular intake. (1) C57BL/6J male and female mice (n = 33) were randomly subdivided into: SHAM (n = 7), MI (n = 15) and MI fed for 4weeks with a normal chow supplemented with Tuscany SGJ (25% vol/vol, 200µl/per day) (MI + SGJ, n = 11). Echocardiography and histological analyses were performed. Myocardial NPs transcriptional profile was investigated by Real-Time PCR. (2) MCEC-1 were treated for 24h with a pool of SGJ small RNAs and cell viability under 24h exposure to H2O2 was evaluated by MTT assay. (3) Human blood samples were collected from seven subjects before and after the 7days' intake of Tuscany SGJ. NPs and miRNA transcriptional profile were investigated by Real-Time PCR in MCEC-1 and human blood. Our experimental data, obtained in a multimodal pipeline, suggest that the long-term intake of SGJ promotes an adaptive response of the myocardium to the ischemic microenvironment through the modulation of the cardiac CNP/NPR-B/NPR-C system. Our results open new avenue in the development of functional foods aimed at enhancing cardioprotection of infarcted hearts through action on the myocardial epigenome.