Abstract
MicroRNAs (miRNAs/miRs) such as miR-1, miR-133a, miR-133b, miR-135a, and miR-29b play a key role in many cardiac pathological remodeling processes, including apoptosis, fibrosis, and arrhythmias, after a myocardial infarction (MI). Dietary flaxseed has demonstrated a protective effect against an MI. The present study was carried out to test the hypothesis that dietary flaxseed supplementation before and after an MI regulates the expression of above-mentioned miRNAs to produce its cardioprotective effect. Animals were randomized after inducing MI by coronary artery ligation into: (a) sham MI with normal chow, (b) MI with normal chow, and (c–e) MI supplemented with either 10% milled flaxseed, or 4.4% flax oil enriched in alpha-linolenic acid (ALA), or 0.44% flax lignan secoisolariciresinol diglucoside. The feeding protocol consisted of 2 weeks before and 8 weeks after the surgery. Dietary flax oil supplementation selectively upregulated the cardiac expression of miR-133a, miR-135a, and miR-29b. The levels of collagen I expression were reduced in the flax oil group. We conclude that miR-133a, miR-135a, and miR-29b are sensitive to dietary flax oil, likely due to its rich ALA content. The cardioprotective effect of flaxseed in an MI could be due to modulation of these miRNAs.
Highlights
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, and according to the latest estimates by the Heart Disease and Stroke Statistics—2019 update, approximately 1 of every 3 deaths occur due to CVD
Animals were randomized into five groups: (a) sham myocardial infarction (MI) fed normal chow, (b) MI fed normal chow, (c) MI fed chow supplemented with 10% milled flaxseed, (d) MI fed chow supplemented with 4.4% flax oil enriched in alpha-linolenic acid (Oil), and (e) MI fed chow supplemented with the flax lignan secoisolariciresinol diglucoside (SDG) (0.44%)
The ratios of n-6 to n-3 fatty acid levels were significantly lowered in the flaxseed and the flax oil supplemented diets compared to the control diet, Figure 1
Summary
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, and according to the latest estimates by the Heart Disease and Stroke Statistics—2019 update, approximately 1 of every 3 deaths occur due to CVD. MiRNAs can either promote or inhibit apoptosis of cardiomyocytes, they can modulate angiogenesis, alter cardiac regeneration and reprogram cardiac fibroblasts into cardiomyocytes [9] These effects clearly support a relationship between altered miRNA expression and ischemic heart disease. In view of the above discussion of the impact of miRNAs on cardiac performance under pathological challenge, it is possible that dietary flaxseed may alter miRNA expression and, affect myocardial adaptive processes In support of this hypothesis, diet is known to induce significant cardioprotective effects via a direct action on the epigenome [23]. The current investigation was performed to test the hypothesis that flaxseed supplementation exerts its cardioprotective effect by modulating the expression of miR-1, miR-133a, miR-133b, miR-135a, and miR-29b, which are involved in the adverse cardiac remodeling process after an MI
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