Chaturvedi Pankaj, Kamat Pradip K, Kalani Anuradha, Familtseva Anastasia, Tyagi Suresh C
Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky.
Department of Anesthesiology, University of Florida, Gainesville, Florida.
J Cell Physiol. 2016 Jul;231(7):1554-61. doi: 10.1002/jcp.25247. Epub 2016 Feb 11.
High methionine diet (HMD) for example red meat which includes lamb, beef, pork can pose cardiac threat and vascular dysfunction but the mechanisms are unclear. We hypothesize that a diet rich in methionine can malfunction the cardiovascular system in three ways: (1) by augmenting oxidative stress; (2) by inflammatory manifestations; and (3) by matrix/vascular remodeling. To test this hypothesis we used four groups of mice: (1) WT; (2) WT + methionine; (3) CBS(+/-) ; (4) CBS(+/-) +methionine. We observed high oxidative stress in mice fed with methionine which was even higher in CBS(+/-) and CBS(+/-) +methionine. Higher oxidative stress was indicated by high levels of SOD-1 in methionine fed mouse hearts whereas IL-1β, IL-6, TNFα, and TLR4 showed high inflammatory manifestations. The upregulated levels of eNOS/iNOS and upregulated levels of MMP2/MMP9 along with high collagen deposition indicated vascular and matrix remodeling in methionine fed mouse. We evaluated the cardiac function which was dysregulated in the mice fed with HMD. These mice had decreased ejection fraction and left ventricular dysfunction which subsequently leads to adverse cardiac remodeling. In conclusion, our study clearly shows that HMD poses a cardiac threat by increasing oxidative stress, inflammatory manifestations, matrix/vascular remodeling, and decreased cardiac function.
例如,富含蛋氨酸的饮食(HMD),如包括羊肉、牛肉、猪肉在内的红肉,会对心脏构成威胁并导致血管功能障碍,但其机制尚不清楚。我们推测,富含蛋氨酸的饮食会通过三种方式使心血管系统功能失调:(1)通过增强氧化应激;(2)通过炎症表现;(3)通过基质/血管重塑。为了验证这一假设,我们使用了四组小鼠:(1)野生型(WT);(2)野生型+蛋氨酸;(3)胱硫醚β-合成酶(CBS)杂合子(+/-);(4)CBS(+/-)+蛋氨酸。我们观察到,喂食蛋氨酸的小鼠体内氧化应激水平较高,在CBS(+/-)和CBS(+/-)+蛋氨酸组中甚至更高。喂食蛋氨酸的小鼠心脏中,超氧化物歧化酶-1(SOD-1)水平升高表明氧化应激较高,而白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNFα)和Toll样受体4(TLR4)则表现出较高的炎症表现。内皮型一氧化氮合酶(eNOS)/诱导型一氧化氮合酶(iNOS)水平上调以及基质金属蛋白酶2(MMP2)/基质金属蛋白酶9(MMP9)水平上调,再加上高胶原蛋白沉积,表明喂食蛋氨酸的小鼠出现血管和基质重塑。我们评估了心脏功能,发现喂食HMD的小鼠心脏功能失调。这些小鼠的射血分数降低,左心室功能障碍,随后导致不良的心脏重塑。总之,我们的研究清楚地表明,HMD通过增加氧化应激、炎症表现、基质/血管重塑和心脏功能下降对心脏构成威胁。