Lopaschuk Gary D
Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, 423 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada.
Curr Opin Investig Drugs. 2004 Mar;5(3):290-4.
Fatty acids are a major source of fuel used by the heart to provide large amounts of energy necessary to sustain contractile function. In the healthy heart, a balance between fatty acid and carbohydrate use ensures that energy supply to the heart matches demand. However, myocardial ischemia causes profound changes in metabolism, including alterations in glucose and fatty acid metabolism that can lead to excessive myocardial fatty acid oxidation, which occurs at the expense of glucose oxidation. This contributes to cellular acidosis, a decrease in cardiac efficiency and contractile dysfunction in the ischemic heart. Inhibition of fatty acid oxidation has recently emerged as a promising approach to the prevention of these adverse effects of fatty acids. As a result, a number of key enzymes involved in the metabolism of fatty acids are potential targets for therapeutic intervention in myocardial ischemia. This includes inhibition of fatty acid uptake into the myocyte, inhibition of mitochondrial fatty acid uptake and direct inhibition of fatty acid beta-oxidation. This review describes these potential targets for modulation of energy metabolism in the heart.
脂肪酸是心脏用于提供维持收缩功能所需大量能量的主要燃料来源。在健康心脏中，脂肪酸与碳水化合物利用之间的平衡可确保心脏的能量供应与需求相匹配。然而，心肌缺血会导致代谢发生深刻变化，包括葡萄糖和脂肪酸代谢的改变，这可能导致心肌脂肪酸过度氧化，而这是以葡萄糖氧化为代价的。这会导致细胞酸中毒、心脏效率降低以及缺血性心脏的收缩功能障碍。抑制脂肪酸氧化最近已成为预防脂肪酸这些不良反应的一种有前景的方法。因此，一些参与脂肪酸代谢的关键酶是心肌缺血治疗干预的潜在靶点。这包括抑制脂肪酸进入心肌细胞、抑制线粒体脂肪酸摄取以及直接抑制脂肪酸β氧化。本综述描述了这些调节心脏能量代谢的潜在靶点。
