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

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 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 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/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 24 h with a pool of SGJ small RNAs and cell viability under 24 h exposure to H2O2 was evaluated by MTT assay. (3) Human blood samples were collected from seven 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

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.

Conclusions

Our results open new avenue in the development of functional foods aimed at enhancing cardioprotection of infarcted hearts through action on the myocardial epigenome.

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References

  1. 1.

    Miller V, Mente A, Dehghan M, Rangarajan S, Zhang X, Swaminathan Dagenais G, Gupta R, Mohan V, Lear S et al (2017) Prospective Urban Rural Epidemiology (PURE) study investigators. Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study. Lancet 390:2037–2049

    PubMed  Article  Google Scholar 

  2. 2.

    Rautiainen S, Levitan EB, Mittleman MA, Wolk A (2015) Fruit and vegetable intake and rate of heart failure: a population-based prospective cohort of women. Eur J Heart Fail 17:20–26

    PubMed  Article  Google Scholar 

  3. 3.

    Tektonidis TG, Åkesson A, Gigante B, Wolk A, Larsson SC (2016) Adherence to a Mediterranean diet is associated with reduced risk of heart failure in men. Eur J Heart Fail 18:253–259

    PubMed  Article  Google Scholar 

  4. 4.

    Bechthold A, Boeing H, Schwedhelm C, Hoffmann G, Knüppel S, Iqbal K, De Henauw S, Michels N, Devleesschauwer B, Schlesinger S, Schwingshackl L (2017) Food groups and risk of coronary heart disease, stroke and heart failure: a systematic review and dose-response meta-analysis of prospective studies. Crit Rev Food Sci Nutr 17:1–20

    Google Scholar 

  5. 5.

    Lionetti V, Tuana BS, Casieri V, Parikh M, Pierce GN (2019) Importance of functional food compounds in cardioprotection through action on the epigenome. Eur Heart J 40:575–582

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS, Pruess HG (2000) Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 148:187–197

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Nassiri-Asl M, Hosseinzadeh H (2009) Review of the pharmacological effects of Vitis vinifera (Grape) and its bioactive compounds. Phytother Res 23:1197–1204

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Xia EQ, Deng GF, Guo YJ, Li HB (2012) Biological activities of polyphenols from grapes. Int J Mol Sci 11:622–646

    Article  CAS  Google Scholar 

  9. 9.

    Folts JD (2002) Potential health benefits from the flavonoids in grape products on vascular disease. Adv Exp Med Biol 505:95–111

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Lekakis J, Rallidis LS, Andreadou I, Vamvakou G, Kazantzoglou G, Magiatis P, Skaltsounis AL, Kremastinos DT (2005) Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil 12:596–600

    PubMed  Google Scholar 

  11. 11.

    Blumberg JB, Vita JA, Chen CY (2015) Concord grape juice polyphenols and cardiovascular risk factors: dose-response relationships. Nutrients 7:10032–10052

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Haseeb S, Alexander B, Baranchuk A (2017) Wine and cardiovascular health: a comprehensive review. Circulation 136:1434–1448

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Georgiev V, Ananga A, Tsolova V (2014) Recent advances and uses of grape flavonoids as nutraceutical. Nutrients 6:391–415

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  14. 14.

    Cho S, Namkoong K, Shin M, Park J, Yang E, Ihm J, Thu VT, Kim HK, Han J (2017) Cardiovascular protective effects and clinical applications of resveratrol. J Med Food 20:1–12

    Article  Google Scholar 

  15. 15.

    Khadem-Ansari MH, Rasmi Y, Ramezani F (2012) Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers. Open Biochem J 4:96–99

    Article  CAS  Google Scholar 

  16. 16.

    Tenore GC, Manfra M, Stiuso P, Coppola L, Russo M, Gomez Monterrey IM, Campiglia F (2012) Antioxidant profile and in vitro cardiac radical-scavenging versus pro-oxidant effects of commercial red grape juices (Vitis vinifera L. cv. Aglianico N.). J Agric Food Chem 60:9680–9687

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    de Freitas RB, Boligon AA, Rovani BT, Piana M, de Brum TF, da Silva Jesus R, Rother FC, Alves NM, Teixeira da Rocha JB, Athayde ML, Barrio JP, de Andrade ER, de Freitas Bauerman L (2013) Effect of black grape juice against heart damage from acute gamma TBI in rats. Molecules 18:12154–12167

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  18. 18.

    Lionetti V (2016) The unexpected cardioprotection by epigenetic foods. JSAS 18:1–9

    Google Scholar 

  19. 19.

    Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY (2012) Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res 22:107–126

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Baier SR, Nguyen C, Xie F, Wood JR, Zempleni J (2014) MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers. J Nutr 144:495–500

    Google Scholar 

  21. 21.

    Yang J, Farmer LM, Agyekum AA, Hirschi KD (2015) Detection of dietary plant-based small RNAs in animals. Cell Res 25:517–520

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Cabrera-Fuentes HA, Aragones J, Bernhagen J, Boening A, Boisvert WA, Bøtker HE, Bulluck H, Cook S, Di Lisa F, Engel FB et al (2016) From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”. Basic Res Cardiol 111:69

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  23. 23.

    Luo Y, Wang P, Wang X, Wang Y, Mu Z, Li Q, Fu Y, Xiao J, Li G, Ma Y, Gu Y, Jin L, Ma J, Tang Q, Jiang A, Li X, Li M (2017) Detection of dietetically absorbed maize-derived microRNAs in pigs. Sci Rep 7:645

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  24. 24.

    Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS et al (2012) Executive summary: heart disease and stroke statistics - 2012 update: a report from the American Heart Association. Circulation 125:188–197

    PubMed  Article  Google Scholar 

  25. 25.

    Westman PC, Lipinski MJ, Luger D, Waksman R, Bonow RO, Wu E, Epstein SE (2016) Inflammation as a driver of adverse left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 67:2050–2060

    PubMed  Article  Google Scholar 

  26. 26.

    Sutton MG, Sharpe N (2000) Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 101:2981–2988

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Lionetti V, Bianchi G, Recchia FA, Ventura C (2010) Control of autocrine and paracrine myocardial signals: an emerging therapeutic strategy in heart failure. Heart Fail Rev 15:531–542

    PubMed  Article  Google Scholar 

  28. 28.

    Mann DL (2005) Left ventricular size and shape: determinants of mechanical signal transduction pathways. Heart Fail Rev 10:95–100

    PubMed  Article  Google Scholar 

  29. 29.

    Levis ER, Gardner DG, Samson WK (1998) Natriuretic peptides. N Eng J Med 339:3218

    Google Scholar 

  30. 30.

    Del Ry S, Cabiati M, Clerico A (2013) Recent advances on natriuretic peptide system: new promising therapeutic targets for the treatment of heart failure. Pharmacol Res 76:190–198

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Soeki T, Kishimoto I, Okumura H, Tokudome T, Horio T, Kangawa MK (2005) C type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction. J Am Coll Cardiol 45:608–616

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Wang Y, de Waard MC, Sterner-Kock A, Stepan H, Schultheiss HP, Walther DJT (2007) Cardiomyocyte-restricted over-expression of C-type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice. Eur J Heart Fail 9:548–557

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Del Ry S, Cabiati M, Vozzi F, Battolla B, Caselli C, Forini F, Segnani C, Prescimone T, Giannessi D, Mattii L (2011) Expression of C-type natriuretic peptide and its receptor NPR-B in cardiomyocytes. Peptides 32:1713–1718

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Suga S, Nakao K, Itoh H, Komatsu Y, Ogawa Y, Hama N, Imura H (1992) Endothelial production of C-type natriuretic peptide and its marked augmentation by transforming growth factor-beta. Possible existence of “vascular natriuretic peptide system”. J Clin Invest 90:1145–1149

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Schulz S (2005) C-type natriuretic peptide and guanylyl cyclase B receptor. Peptides 26:1024–1034

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Costa MA, Elesgaray R, Caniffi C, Fellet A, Arranz C (2007) Role of cardiovascular nitric oxide system in C-type natriuretic peptide effects. Biochem Biophys Res Commun 359:180–186

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Caniffi C, Elesgaray R, Gironacci M, Arranz C, Costa MA (2010) C-type natriuretic peptide effects on cardiovascular nitric oxide system in spontaneously hypertensive rats. Peptides 31:1309–1318

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Barile L, Lionetti V, Cervio E, Matteucci M, Gherghiceanu M, Popescu LM, Torre T, Siclari F, Moccetti T, Vassalli G (2014) Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovasc Res 103:530–541

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Huang WQ, Wei P, Lin RQ, Huang F (2017) Protective Effects of MicroRNA-22 against endothelial cell injury by targeting nlrp3 through suppression of the inflammasome signaling pathway in a rat model of coronary heart disease. Cell Physiol Biochem 43:1346–1358

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Del Ry S, Cabiati M, Martino A, Cavallini C, Caselli C, Aquaro GD, Battolla B, Prescimone T, Giannessi D, Mattii L, Lionetti V (2013) High concentration of C-type natriuretic peptide promotes VEGF-dependent vasculogenesis in the remodeled region of infarcted swine heart with preserved left ventricular ejection fraction. Int J Cardiol 168:2426–2434

    PubMed  Article  Google Scholar 

  41. 41.

    Casieri V, Matteucci M, Cavallini C, Torti M, Torelli M, Lionetti V (2017) Long-term intake of pasta containing barley (1-3) Beta-d-glucan increases neovascularization-mediated cardioprotection through endothelial upregulation of vascular endothelial growth factor and parkin. Sci Rep 7:13424

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  42. 42.

    Hecker PA, Lionetti V, Ribeiro RF Jr, Rastogi S, Brown BH, O’Connell KA, Cox JW, Shekar KC, Gamble DM, Sabbah HN, Leopold JA, Gupte SA, Recchia FA, Stanley WC (2013) Glucose 6-phosphate dehydrogenase deficiency increases redox stress and moderately accelerates the development of heart failure. Circ Heart Fail 6:118–126

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Belli KJ, Pinto DLP, Bertolini E, Fasoli M, Zenoni S, Tornielli GB, Pezzotti M, Meyers BC, Farina L, Pè ME, Mica E (2015) miRVine: a microRNA expression atlas of grapevine based on small RNA sequencing. BMC Genom 16:393. https://doi.org/10.1186/s12864-015-1610-5

    CAS  Article  Google Scholar 

  44. 44.

    Pinto DLP, Brancadoro L, Dal Santo S, De Lorenzis G, Pezzotti M, Meyers BC, Pè ME, Mica E (2016) The Influence of Genotype and Environment on Small RNA Profiles in Grapevine Berry. Front Plant Sci 7:1459

    Google Scholar 

  45. 45.

    Cabiati M, Sabatino L, Caruso R, Verde A, Caselli C, Prescimone T, Giannessi D, Del Ry S (2013) C-type natriuretic peptide transcriptomic profiling increases in human leukocytes of patients with chronic heart failure as a function of clinical severity. Peptides 47:110–114

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Del Ry S, Cabiati M, Lionetti V, Emdin M, Recchia FA, Giannessi D (2008) Expression of C-type natriuretic peptide and of its receptor NPR-B in normal and failing heart. Peptides 29:2208–2215

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Del Ry S, Cabiati M, Lionetti V, Simioniuc A, Caselli C, Prescimone T, Emdin M, Giannessi D (2009) Asymmetrical myocardial expression of natriuretic peptides in pacing-induced heart failure. Peptides 30:1710–1713

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Dushpanova A, Agostini A, Ciofini E, Cabiati M, Casieri V, Matteucci M, Del Ry S, Clerico A, Berti S, Lionetti V (2016) Gene silencing of endothelial von Willebrand factor attenuates angiotensin II-induced endothelin-1 expression in porcine aortic endothelial cells. Sci Rep 6:30048

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum Information for publications of Quantitative Real-Time PCR experiments. Clin Chem 55:611–622

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative rt-pcr data by geometric averaging of multiple internal control genes. Genome Biol 3(7):research0034.1–0034.11

    Article  Google Scholar 

  51. 51.

    Martino A, Cabiati M, Campan M, Prescimone T, Minocci D, Caselli C, Rossi AM, Giannessi D, Del Ry S (2011) Selection of reference genes for normalization of real-time PCR data in minipig heart failure model and evaluation of TNF-α mRNA expression. J Biotechnol 153:92–99

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Cabiati M, Raucci S, Caselli C, Guzzardi MA, D’Amico A, Prescimone T, Giannessi D, Del Ry S (2012) Tissue-specific selection of stable reference genes for real-time PCR normalization in an obese rat model. J Mol Endocrinol 48:251–260

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Yarmarkovich M, Hirschi KD (2015) Digesting dietary miRNA therapeutics. Oncotarget 6:13848–13849

    PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Zempleni J, Baier SR, Howard KM, Cui J (2015) Gene regulation by dietary microRNAs. Can J Physiol Pharmacol 93:1097–1102

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Hirschi KD, Pruss GJ, Vance V (2015) Dietary delivery: a new avenue for microRNA therapeutics? Trends Biotechnol 33:431–432

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    Wagner AE, Piegholdt S, Ferraro M, Pallauf K, Rimbach G (2015) Food derived microRNAs. Food Funct 6:714–718

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Clerico A, Giannoni A, Vittorini S, Passino C (2011) Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones. Am J Physiol Heart Circ Physiol 301:H12–H20

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Gardner DG (2003) Natriuretic peptides: markers or modulators of cardiac hypertrophy? Trends Endocrinol Metab 14:411–416

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Kuhn M, Voss M, Mitko M, Stypmann J, Schmid C, Kawaguchi N, Grabellus F, Baba HA (2004) Left ventricular assist device support reverses altered cardiac expression and function of natriuretic peptides and receptors in end-stage heart failure. Cardiovasc Res 64:308–314

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Moilanen AM, Rysä J, Mustonen E, Serpi R, Aro J, Tokola H, Leskinen H, Manninen A, Levijoki J, Vuolteenaho O, Ruskoaho H (2011) Intramyocardial BNP gene delivery improves cardiac function through distinct context-dependent mechanisms. Circ Heart Fail 4:483–495

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Wu LH, Zhang Q, Zhang S, Meng LY, Wang YC, Sheng CJ (2018) Effects of gene knockdown of CNP on ventricular remodeling after myocardial ischemia-reperfusion injury through NPRB/Cgmp signaling pathway in rats. J Cell Biochem 119:1804–1818

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Hobbs A, Foster P, Prescott C, Scotland R, Ahluwalia A (2004) Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for endothelium-derived C-type natriuretic peptide. Circulation 110:1231–1235

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Hystad ME, Øie E, GrØgaard HK, Kuusnemi K, Vuolteenaho O, Attramadal H, Hall C (2001) Gene expression of natriuretic peptides and their receptors type-A and -C after myocardial infarction in rats. Scand J Clin Lab Invest 61:139–150

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Chun YS, Hyun JY, Kwak YG, Kim IS, Kim CH, Choi E, Kim MS, Park JW (2003) Hypoxic activation of the atrial natriuretic peptide gene promoter through direct and indirect actions of hypoxia-inducible factor-1. Biochem J 370:149–157

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. 65.

    Knowles JW, Esposito G, Mao L, Hagaman JR, Fox JE, Smithies O, Rockman HA, Maeda N (2001) Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A–deficient mice. J Clin Invest 107:975–984

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

    Zhang J, Zhang BH, Yu YR, Tang CS, Qi YF (2011) Adrenomedullin protects against fructose-induced insulin resistance and myocardial hypertrophy in rats. Peptides 32:1415–1421

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Cavasin MA, Tao Z, Menon S, Yang XP (2004) Gender differences in cardiac function during early remodeling after acute myocardial infarction in mice. Life Sci 75:2181–2192

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Fang L, Gao XM, Moore XL, Kiriazis H, Su Y, Ming Z, Lim YL, Dart AM, Du XJ (2007) Differences in inflammation, MMP activation and collagen damage account for gender difference in murine cardiac rupture following myocardial infarction. J Mol Cell Cardiol 43:535–544

    CAS  PubMed  Article  Google Scholar 

  69. 69.

    van Rooij E, Fielitz J, Sutherland LB, Thijssen VL, Dimaio MJ, Shelton J, De Windt LJ, Hill JA, Olson EN (2010) Myocyte enhancer factor 2 and class II histone deacetylases control a gender-specific pathway of cardioprotection mediated by the estrogen receptor. Circ Res 106:155–165

    PubMed  Article  CAS  Google Scholar 

  70. 70.

    Acuff CG, Huang H, Steinhelper ME (1997) Estradiol induces C-type natriuretic peptide gene expression in mouse uterus. Am J Physiol 273:H2672–H2677

    CAS  PubMed  Google Scholar 

  71. 71.

    Klinge CM, Risinger KE, Watts MB, Beck V, Eder R, Jungbauer A (2003) Estrogenic activity in white and red wine extracts. J Agric Food Chem 51:1850–1857

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Genova G, Tosetti R, Tonutti P (2016) Berry ripening, pre-processing and thermal treatments affect the phenolic composition and antioxidant capacity of grape (Vitis vinifera L.) juice. J Sci Food Agric 96:664–671

    CAS  PubMed  Article  Google Scholar 

  73. 73.

    Lizotte E, Grandy SA, Tremblay A, Allen BG, Fiset C (2009) Expression, distribution and regulation of sex steroid hormone receptors in mouse heart. Cell Physiol Biochem 23:75–86

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Kuramochi Y, Cote GM, Guo X, Lebrasseur NK, Cui L, Liao R, Sawyer DB (2004) Cardiac endothelial cells regulate reactive oxygen species-induced cardiomyocyte apoptosis through neuregulin-1beta/erbB4 signaling. J Biol Chem 279:51141–51147

    CAS  PubMed  Article  Google Scholar 

  75. 75.

    Casieri V, Agostini S, Lionetti V (2014) Epigenetic modulation of myocardial angiogenic balance: an emerging therapeutic perspective for adult failing heart. Curr Angiogenes 3:3–10

    Article  Google Scholar 

  76. 76.

    Sun L, Yau HY, Wong WY, Li RA, Huang Y, Yao X (2012) Role of TRPM2 in H2O2-induced cell apoptosis in endothelial cells. PLoS One 7:e43186

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    Liang H, Zhang S, Fu Z, Wang Y, Wang N, Liu Y, Zhao C, Wu J, Hu Y, Zhang J, Chen X, Zen K, Zhang CY (2015) Effective detection and quantification of dietetically absorbed plant microRNAs in human plasma. J Nutr Biochem 26:505–512

    CAS  PubMed  Article  Google Scholar 

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Acknowledgements

This study was conducted within the context of the project entitled Cardio.MIR.San.To (Bando Nutraceutica DD 650/2014), supported by the Regione Toscana (Tuscany Region). We are grateful to Fattoria Viticcio (Greve in Chianti, Italy) for technical support.

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Contributions

SDR, VL, BS, MEP: designed research; BS, MC, MM, CP: conducted research; SDR, VL, BS: analyzed and interpreted data and wrote the manuscript. SDR, VL, MEP had primary responsibility for the final content. All authors read and approved the final manuscript.

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Correspondence to S. Del Ry.

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Svezia, B., Cabiati, M., Matteucci, M. et al. Tuscany Sangiovese grape juice imparts cardioprotection by regulating gene expression of cardioprotective C-type natriuretic peptide. Eur J Nutr 59, 2953–2968 (2020). https://doi.org/10.1007/s00394-019-02134-x

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Keywords

  • Sangiovese grape juice
  • Functional food
  • Natriuretic peptide system
  • C-type natriuretic peptide
  • Plant miRNAs
  • Myocardial infarction