Moriyama Hidenori, Endo Jin, Ikura Hidehiko, Kitakata Hiroki, Momoi Mizuki, Shinya Yoshiki, Ko Seien, Ichihara Genki, Hiraide Takahiro, Shirakawa Kohsuke, Anzai Atsushi, Katsumata Yoshinori, Sano Motoaki
Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-City, Tokyo 160-8582, Japan.
Metabolites. 2022 Feb 25;12(3):210. doi: 10.3390/metabo12030210.
Fatty acids (FAs) have structural and functional diversity. FAs in the heart are closely associated with cardiac function, and their qualitative or quantitative abnormalities lead to the onset and progression of cardiac disease. FAs are important as an energy substrate for the heart, but when in excess, they exhibit cardio-lipotoxicity that causes cardiac dysfunction or heart failure with preserved ejection fraction. FAs also play a role as part of phospholipids that compose cell membranes, and the changes in mitochondrial phospholipid cardiolipin and the FA composition of plasma membrane phospholipids affect cardiomyocyte survival. In addition, FA metabolites exert a wide variety of bioactivities in the heart as lipid mediators. Recent advances in measurement using mass spectrometry have identified trace amounts of n-3 polyunsaturated fatty acids (PUFAs)-derived bioactive metabolites associated with heart disease. n-3 PUFAs have a variety of cardioprotective effects and have been shown in clinical trials to be effective in cardiovascular diseases, including heart failure. This review outlines the contributions of FAs to cardiac function and pathogenesis of heart diseases from the perspective of three major roles and proposes therapeutic applications and new medical perspectives of FAs represented by n-3 PUFAs.
脂肪酸(FAs)具有结构和功能多样性。心脏中的脂肪酸与心脏功能密切相关,其质或量的异常会导致心脏病的发生和发展。脂肪酸作为心脏的能量底物很重要,但过量时,它们会表现出心脏脂毒性,导致心脏功能障碍或射血分数保留的心力衰竭。脂肪酸还作为构成细胞膜的磷脂的一部分发挥作用,线粒体磷脂心磷脂的变化以及质膜磷脂的脂肪酸组成会影响心肌细胞的存活。此外,脂肪酸代谢产物作为脂质介质在心脏中发挥多种生物活性。使用质谱法进行测量的最新进展已鉴定出与心脏病相关的痕量n-3多不饱和脂肪酸(PUFAs)衍生的生物活性代谢产物。n-3多不饱和脂肪酸具有多种心脏保护作用,并且在临床试验中已证明对包括心力衰竭在内的心血管疾病有效。本综述从三个主要作用的角度概述了脂肪酸对心脏功能和心脏病发病机制的贡献,并提出了以n-3多不饱和脂肪酸为代表的脂肪酸的治疗应用和新的医学观点。