Long-term Intake of Pasta Containing Barley (1\u20133)Beta-D-Glucan Increases Neovascularization-mediated Cardioprotection through Endothelial Upregulation of Vascular Endothelial Growth Factor and Parkin

Valentina Casieri,Marco Matteucci,Claudia Cavallini,Milena Torti,Vincenzo Lionetti,Michele Torelli

doi:10.1038/s41598-017-13949-1

Abstract

Barley (1–3)β-D-Glucan (BBG) enhances angiogenesis. Since pasta is very effective in providing a BBG-enriched diet, we hypothesized that the intake of pasta containing 3% BBG (P-BBG) induces neovascularization-mediated cardioprotection. Healthy adult male C57BL/6 mice fed P-BBG (n = 15) or wheat pasta (Control, n = 15) for five-weeks showed normal glucose tolerance and cardiac function. With a food intake similar to the Control, P-BBG mice showed a 109% survival rate (P < 0.01 vs. Control) after cardiac ischemia (30 min)/reperfusion (60 min) injury. Left ventricular (LV) anion superoxide production and infarct size in P-BBG mice were reduced by 62 and 35% (P < 0.0001 vs. Control), respectively. The capillary and arteriolar density of P-BBG hearts were respectively increased by 12 and 18% (P < 0.05 vs. Control). Compared to the Control group, the VEGF expression in P-BBG hearts was increased by 87.7% (P < 0.05); while, the p53 and Parkin expression was significantly increased by 125% and cleaved caspase-3 levels were reduced by 33% in P-BBG mice. In vitro, BBG was required to induce VEGF, p53 and Parkin expression in human umbelical vascular endothelial cells. Moreover, the BBG-induced Parkin expression was not affected by pifithrin-α (10 uM/7days), a p53 inhibitor. In conclusion, long-term dietary supplementation with P-BBG confers post-ischemic cardioprotection through endothelial upregulation of VEGF and Parkin.

Highlights

Compared to the Control group, the vascular endothelial growth factor (VEGF) expression in pasta containing 3% BBG (P-BBG) hearts was increased by 87.7% (P < 0.05); while, the p53 and Parkin expression was significantly increased by 125% and cleaved caspase-3 levels were reduced by 33% in P-BBG mice
We demonstrated that long-term exposure of human endothelial cells to 3% BBG increases manganese superoxide dismutase (MnSOD) expression and nitric oxide (NO) production, which promote the formation of new vessels[22]
To the best of our knowledge, this is the first study to show in vivo data demonstrating that a sustained dietary intake of pasta enriched with BBG safely increases coronary collaterals, limits the infarct size, and reduces mortality

Summary

Introduction

BBG was required to induce VEGF, p53 and Parkin expression in human umbelical vascular endothelial cells. An individual’s tolerance to the post-ischemic reperfusion insult of the heart depends on the variation in density of the native coronary collaterals[4,5]. These collaterals lead to retrograde perfusion of the obstructed coronary tree by limiting the magnitude of the myocardial ischemia/reperfusion (I/R) injury in animal models[6] and in www.nature.com/scientificreports/. We demonstrated that long-term exposure of human endothelial cells to 3% BBG increases manganese superoxide dismutase (MnSOD) expression and nitric oxide (NO) production, which promote the formation of new vessels[22]. A previous in vitro study revealed that VEGF induces endothelial MnSOD expression[23], it is still unknown whether sustained dietary intake of BBG promotes cardioprotection in vivo through endothelial upregulation of VEGF and Parkin

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Conclusion