High Methionine Diet Poses Cardiac Threat: A Molecular Insight

Abstract

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.

Insulin‐like growth factors and their potential role in cardiac epigenetics

“…It has been suggested that a diet rich in methionine can induce CVD by oxidative stress, inflammatory manifestations and vascular remodeling. Mice fed with methionine developed CVD with LV dysfunction marked by higher levels of superoxide dismutase-1 in the hearts, while interleukin (IL)-1, IL-6, tumour necrosis factor a and TLR4 (toll-like receptor 4) showed a significant inflammatory profile [62,129]. The upregulated levels of eNOS/iNOS and MMP2/MMP9 beside high collagen deposition indicated vascular remodeling in same methionine fed mouse model [129].…”

Sexual dimorphism in cardiac transcriptome associated with a troponin C murine model of hypertrophic cardiomyopathy

“…A diet high in methionine has been previously established as a cardiac threat due to the risk of accumulative oxidative stress, inflammation, vascular remodeling, and decreased cardiac function (Chaturvedi, Kamat, Kalani, Familtseva, & Tyagi, 2016). Since our study exhibited downregulation of methionine degradation we posit that this may be a contributing factor underlying disease manifestations in the cTnC‐A8V mice much in the same way that a high methionine diet has been linked to cardiac damage and altered function.…”

Metabolic Regulation of Methionine Restriction in Diabetes

“…In addition, methionine can indirectly enhance antioxidant function via improvement of Cys and GSH metabolism and mediation of oxidative PPP. Nevertheless, a dietary excess of methionine after increased homocysteine and altered DNA methylation shows a pro‐oxidant effect and is involved in various pathological developments . Thus, it is not yet clear which dosage of methionine to exert antioxidant function and avoid oxidative stress will be useful in the treatment of diseases related to oxidative stress.…”