Purpose: 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 MI; 2) in vitro the response to SGJ small RNAs of murine MCEC-1 under physiological and ischemic condition; 3) the activation of the CNP/NPR-B/NPR-C in healthy human subjects after 7 days’ SGJ regular intake. Methods: 1) C57BL/6J male and female mice (n=33) were randomly subdivided into: Sham (n=7), MI (n=15) and MI fed for 4 weeks with a normal chow supplemented with Tuscany SGJ (25% vol/vol, 200 µl/die) (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 7 subjects before and after the 7 days’ intake of Tuscany SGJ. NPs and miRNA transcriptional profile were investigated by Real-Time PCR in MCEC-1 and human blood. Results: We found that regular diet supplementation with SGJ rich of miRNAs promotes protection of ischemic heart against myocardial infarction in male rather than female mice through the induction of myocardial CNP/NPR-B/NPR-C system. In vitro, SGJ-derived miRNAs preserved endothelial cell viability under oxidative stress. In human subjects fed with SGJ, the maintenance of circulating grape microRNAs levels was related to higher plasma levels of CNP mRNA and subsequent counter-regulation of NPR-B gene expression. Conclusions: Our experimental data obtained in a multimodal translational pipeline open new avenue in the development of functional foods aimed at enhancing cardioprotection of infarcted hearts through action on the myocardial epigenome.
Tuscany Sangiovese Grape juice imparts cardioprotection by regulating gene expression of Cardioprotective C-Type Natriuretic Peptide.
Svezia B;Matteucci M;Passino C;Pè ME;Lionetti V
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2020-01-01
Abstract
Purpose: 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 MI; 2) in vitro the response to SGJ small RNAs of murine MCEC-1 under physiological and ischemic condition; 3) the activation of the CNP/NPR-B/NPR-C in healthy human subjects after 7 days’ SGJ regular intake. Methods: 1) C57BL/6J male and female mice (n=33) were randomly subdivided into: Sham (n=7), MI (n=15) and MI fed for 4 weeks with a normal chow supplemented with Tuscany SGJ (25% vol/vol, 200 µl/die) (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 7 subjects before and after the 7 days’ intake of Tuscany SGJ. NPs and miRNA transcriptional profile were investigated by Real-Time PCR in MCEC-1 and human blood. Results: We found that regular diet supplementation with SGJ rich of miRNAs promotes protection of ischemic heart against myocardial infarction in male rather than female mice through the induction of myocardial CNP/NPR-B/NPR-C system. In vitro, SGJ-derived miRNAs preserved endothelial cell viability under oxidative stress. In human subjects fed with SGJ, the maintenance of circulating grape microRNAs levels was related to higher plasma levels of CNP mRNA and subsequent counter-regulation of NPR-B gene expression. Conclusions: Our experimental data obtained in a multimodal translational pipeline open new avenue in the development of functional foods aimed at enhancing cardioprotection of infarcted hearts through action on the myocardial epigenome.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
