Methionine-supplemented diet affects the expression of cardiovascular disease-related genes and increases inflammatory cytokines in mice heart and liver

Abstract

Some important environmental factors that influence the development of cardiovascular diseases (CVD) include tobacco, excess alcohol, and unhealthy diet. Methionine obtained from the diet participates in the synthesis of DNA, proteins, lipids and affects homocysteine levels, which is associated with the elevated risk for CVD development. Therefore, the aim of this study was to investigate the manner in which dietary methionine might affect cellular mechanisms underlying CVD occurrence. Swiss albino mice were fed either control (0.3% DL-methionine), methionine-supplemented (2% DL-methionine), or a methionine-deprived diet (0% DL-methionine) over a 10-week period. The parameters measured included plasma homocysteine concentrations, oxidative stress by reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, levels of inflammatory cytokines IL-1ß, TNF-α, and IL-6, as well as expression of genes associated with CVD. The levels of apolipoprotein A5 (APOA5), a regulator of plasma triglycerides, were measured. The methionine-supplemented diet increased oxidative stress by lowering the GSH/GSSG ratio in heart tissues and decreased expression of the genes Apob, Ctgf, Serpinb2, Spp1, Il1b, and Sell, but elevated expression of Thbs4, Tgfb2, Ccr1, and Vegfa. Methionine-deprived diet reduced expression of Col3a1, Cdh5, Fabp3, Bax, and Hbegf and increased expression of Sell, Ccl5, Itga2, Birc3, Msr1, Bcl2a1a, Il1r2, and Selp. Methionine-deprived diet exerted pro-inflammatory consequences as evidenced by elevated levels of cytokines IL-1ß, TNF-α, and IL-6 noted in liver. Methionine-supplemented diet increased hepatic IL-6 and cardiac TNF-α. Both methionine supplementation and deprivation lowered hepatic levels of APOA5. In conclusion, data demonstrated that a methionine-supplemented diet modulated important biological processes associated with high risk of CVD development.

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

“…However, methionine supplementation in the diet specifically increases mitochondrial radical oxygen species production and mitochondrial DNA oxidative damage [ 277 , 295 , 296 , 297 ]. Furthermore, these biological activities of methionine provoke many deleterious effects [ 298 , 299 , 300 ]. These biological activities seem to be due to excess methionine or SAM.…”

Homocysteine as a Predictor of Paroxysmal Atrial Fibrillation-Related Events: A Scoping Review of the Literature

“…As the development of AF seems to be a result of the combination of a plethora of risk factors and comorbidities, oxidative stress has been associated with incident AF, while oxidative stress-induced atrial remodeling is considered the most common underlying mechanism; according to several reports, hyperhomocysteinemia has been linked with endothelial dysfunction, thus it represents an important factor for cardiovascular morbidity and mortality [ 93 , 94 ]. We were able to locate a total of 26 reports assessing oxidative stress as a potential mechanism of Hcy-induced cardiotoxicity [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 48 , 49 , 50 , 95 ]. Of these, 25 trials reported a positive correlation between Hcy and cardiomyocyte oxidative stress, while only one report failed to demonstrate oxidative stress as a cause of electron transport chain dysfunction, possibly due to an increased expression of the other protective mitochondrial proteins [ 41 ].…”

Identification and validation of genes associated with aging‐related cardiovascular disease

“…Methionine obtained from the diet participates in the synthesis of DNA, proteins, and lipids and affects HBEGF levels, which is associated with the elevated risk for CVD development. 54 The study conducted by Hongdong Song et al revealed a significant downregulation of HBEGF in the plasma of Kunming mice with respect to skin aging, thereby indicating a direct association between HBEGF and the process of aging. 55 In this study, the expression of HBEGF in CVD group of GSE41177, GSE57345, GSE36961, GSE19151, GSE42955, and GSE58294 datasets was higher than that in nCVD group.…”

“…Heparin‐binding epidermal growth factor‐like growth factor (HBEGF) is a member of the growth factor family and is associated with a variety of diseases. Methionine obtained from the diet participates in the synthesis of DNA, proteins, and lipids and affects HBEGF levels, which is associated with the elevated risk for CVD development 54 . The study conducted by Hongdong Song et al.…”