Schram Kristin, Sweeney Gary
Department of Biology, York University, Toronto, Ontario, Canada.
Trends Cardiovasc Med. 2008 Aug;18(6):199-205. doi: 10.1016/j.tcm.2008.10.001.
Owing to the increased incidence of obesity and its association with heart failure, there is now great interest in elucidating the underlying molecular mechanisms linking these pathologies. Since the discovery of adipose-derived hormones and cytokines, their important regulatory role in myocardial function has emerged. The events that these adipokines can regulate include alterations in myocardial metabolism, cardiomyocyte hypertrophy, cell death, and structure and composition of the extracellular matrix. Here, we focus on the last of these and review current research demonstrating an important role for adipokines, with particular emphasis on leptin and adiponectin, in regulating matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and collagens. From this, it is clear that adipokines are capable of contributing to remodeling of the myocardial extracellular matrix, and the altered adipokine profiles observed in obese individuals may be important in the pathogenesis of heart failure. The feasibility of adipokine manipulation as a potential therapeutic treatment in preventing maladaptive cardiac remodeling is also discussed.
由于肥胖发病率的上升及其与心力衰竭的关联，目前人们对阐明连接这些病症的潜在分子机制有着浓厚兴趣。自脂肪衍生激素和细胞因子被发现以来，它们在心肌功能中的重要调节作用逐渐显现。这些脂肪因子能够调节的事件包括心肌代谢改变、心肌细胞肥大、细胞死亡以及细胞外基质的结构和组成。在此，我们聚焦于其中最后一点，并综述当前研究，这些研究表明脂肪因子，尤其是瘦素和脂联素，在调节基质金属蛋白酶、基质金属蛋白酶组织抑制剂和胶原蛋白方面发挥着重要作用。由此可见，脂肪因子能够促进心肌细胞外基质的重塑，而在肥胖个体中观察到的脂肪因子谱改变可能在心力衰竭的发病机制中具有重要意义。我们还讨论了将调节脂肪因子作为预防心脏适应性不良重塑的潜在治疗方法的可行性。
