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Lactobacillus plantarum Probiotic Induces Nrf2-mediated Antioxidant Signaling and eNOS Expression Resulting in Improvement of Myocardial Diastolic Function
American Journal of Physiology-Heart and Circulatory Physiology ( IF 4.1 ) Pub Date : 2021-09-10 , DOI: 10.1152/ajpheart.00278.2021
Ahmed Aboulgheit 1 , Catherine Karbasiafshar 1 , Zhiqi Zhang 1 , Mohamed Sabra 1 , Guangbin Shi 1 , Aja Tucker 1 , Neel Sodha 1 , M Ruhul Abid 1 , Frank W Sellke 1
Affiliation  

Yorkshire swine were fed standard diet (n=7) or standard diet containing caffeic acid with L. plantarum (n=7) for three weeks. Next, an ameroid constrictor was placed around the left coronary circumflex artery, and the dietary regimens were continued. At fourteen weeks, cardiac function, myocardial perfusion, vascular density, and molecular signaling in ischemic myocardium were evaluated.The L. plantarum-caffeic acid augmented Nrf2 in the ischemic myocardium, and induced Nrf2-regulated antioxidant enzymes heme oxygenase-1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Improved left ventricular diastolic function and decreased myocardial collagen expression were seen in animals receiving the L. plantarum-caffeic acid supplements. The expression of endothelial nitric oxide synthase (eNOS) was increased in ischemic myocardial tissue of the treatment group, while levels of asymmetric dimethyl arginine (ADMA), hypoxia inducible factor 1α (HIF-1α), and phosphorylated MAPK (pMAPK) were decreased. Collateral dependent myocardial perfusion was unaffected while arteriolar and capillary densities were reduced as determined by a-smooth muscle cell actin and CD31 immunofluorescence in ischemic myocardial tissue. Dietary supplementation with L. plantarum and caffeic acid is a safe and effective method of enhancing Nrf2-mediated antioxidant signaling cascade in ischemic myocardium. Although this experimental diet was associated with a reduction in hypoxic stimuli, decreased vascular density and without any change in collateral-dependent perfusion, the net effect of an increase in antioxidant activity and eNOS expression resulted in improvement in diastolic function.

中文翻译:


植物乳杆菌益生菌诱导 Nrf2 介导的抗氧化信号传导和 eNOS 表达,从而改善心肌舒张功能



约克夏猪饲喂标准饲料(n=7)或含有咖啡酸和植物乳杆菌(n=7)的标准饲料三周。接下来,将阿美罗缩窄器放置在左冠状回旋动脉周围,并继续饮食方案。第十四周时,对缺血心肌中的心脏功能、心肌灌注、血管密度和分子信号传导进行了评估。植物乳杆菌-咖啡酸增强了缺血心肌中的 Nrf2,并诱导 Nrf2 调节的抗氧化酶血红素加氧酶-1 (HO- 1)、NADPH 脱氢酶醌 1 (NQO-1) 和硫氧还蛋白还原酶 (TRXR-1)。在接受植物乳杆菌-咖啡酸补充剂的动物中观察到左心室舒张功能改善和心肌胶原蛋白表达减少。治疗组缺血心肌组织中内皮一氧化氮合酶(eNOS)表达增加,不对称二甲基精氨酸(ADMA)、缺氧诱导因子1α(HIF-1α)、磷酸化MAPK(pMAPK)水平降低。根据缺血心肌组织中的α-平滑肌细胞肌动蛋白和CD31免疫荧光测定,侧支依赖性心肌灌注不受影响,而小动脉和毛细血管密度降低。膳食补充植物乳杆菌和咖啡酸是增强缺血心肌中 Nrf2 介导的抗氧化信号级联的安全有效的方法。尽管这种实验性饮食与缺氧刺激减少、血管密度降低有关,并且侧支依赖性灌注没有任何变化,但抗氧化活性和 eNOS 表达增加的净效应导致舒张功能改善。
更新日期:2021-09-10
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