Planavila Anna, Calvo Ricardo Rodríguez, Vázquez-Carrera Manuel
Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Spain.
Mini Rev Med Chem. 2006 Mar;6(3):357-63. doi: 10.2174/138955706776073457.
Cardiac hypertrophy is a response of the heart to a wide range of extrinsic stimuli, such as arterial hypertension, valvular heart disease, myocardial infarction, and cardiomyopathy. Although this process is initially compensatory for an increase workload, its prolongation frequently results in congestive heart failure, arrhythmia, and sudden death. Cardiac hypertrophy is associated with an increase in glucose utilization and a decrease in fatty acid oxidation. It is unclear at present, however, which consequences might result from impaired oxidation of fatty acids in the heart, but several studies have demonstrated that substrate utilization is important in the pathogenesis of cardiac hypertrophy. Here we will focus on the effects of cardiac hypertrophy on the activity of Peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors that regulate the expression of genes involved in fatty acid uptake and oxidation, lipid metabolism and inflammation. Interestingly, activation of the Nuclear Factor (NF)-kappaB signaling pathway, which is one of the most important signal transduction pathways involved in the hypertrophic growth of the myocardium, may suppress the activity of the PPARs, affording a link between cardiac hypertrophy and the fall in fatty acid oxidation in the hypertrophied heart. As a result, inhibition of NF-kappaB activation during cardiac hypertrophy may also ameliorate cardiac fatty acid oxidation, achieving a better improvement in the prevention or inhibition of this pathological process.
心脏肥大是心脏对多种外在刺激的一种反应，如动脉高血压、心脏瓣膜病、心肌梗死和心肌病。尽管这一过程最初是对工作量增加的一种代偿，但长期持续往往会导致充血性心力衰竭、心律失常和猝死。心脏肥大与葡萄糖利用增加和脂肪酸氧化减少有关。然而，目前尚不清楚心脏中脂肪酸氧化受损可能会导致哪些后果，但多项研究表明，底物利用在心脏肥大的发病机制中很重要。在此，我们将重点关注心脏肥大对过氧化物酶体增殖物激活受体（PPARs）活性的影响，PPARs是一种配体激活的转录因子，可调节参与脂肪酸摄取和氧化、脂质代谢及炎症的基因表达。有趣的是，核因子（NF）-κB信号通路的激活是心肌肥大生长过程中最重要的信号转导通路之一，它可能会抑制PPARs的活性，从而在心脏肥大与肥大心脏中脂肪酸氧化减少之间建立起一种联系。因此，在心脏肥大过程中抑制NF-κB的激活也可能改善心脏脂肪酸氧化，在预防或抑制这一病理过程方面取得更好的效果。
