The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
Vascul Pharmacol. 2010 Mar-Apr;52(3-4):113-9. doi: 10.1016/j.vph.2009.11.008. Epub 2009 Dec 11.
Cardiac hypertrophy is a significant independent risk factor for increased mortality, comprising of maladaptive changes in cellular, molecular and metabolic processes that ultimately lead to heart failure. However, cardiac hypertrophy represents a continuum from physiological to compensatory to pathological hypertrophy, so that treatment modalities aimed to shift hypertrophy towards the physiological phenotype would represent an attractive therapeutic strategy. Many of the physiological changes caused by thyroid hormone (TH) treatment may provide direct benefit to the failing heart. Recent experimental studies have shown that TH rapidly activates pro-survival PKB/Akt-mTOR signaling pathways, thus providing cytoprotection and increasing synthesis of normal contractile proteins and metabolic enzymes. TH induces a normal physiological phenotype by binding to nuclear TH receptors that regulate expression of specific genes which promote cell survival and enhance contractile function. Physiological cardiac growth occurs with a coordinated angiogenic response that normalizes myocardial perfusion during hypertrophy, and recent studies support a significant role for TH and its endothelial cell surface integrin receptors and nuclear receptors in neovascularization during TH-induced hypertrophy. The present review examines these molecular mechanisms and intracellular signaling pathways activated in thyroid hormone-induced cardiac hypertrophy that support its therapeutic potential in the treatment of heart disease.
心肌肥厚是导致死亡率增加的一个重要独立危险因素，它包含了细胞、分子和代谢过程的适应性改变，最终导致心力衰竭。然而，心肌肥厚代表了从生理到代偿再到病理性肥厚的连续过程，因此，旨在将肥厚转变为生理表型的治疗方式将代表一种有吸引力的治疗策略。甲状腺激素（TH）治疗引起的许多生理变化可能直接有益于衰竭的心脏。最近的实验研究表明，TH 可快速激活促生存 PKB/Akt-mTOR 信号通路，从而提供细胞保护作用，并增加正常收缩蛋白和代谢酶的合成。TH 通过与核 TH 受体结合，调节特定基因的表达，从而促进细胞存活和增强收缩功能，诱导出正常的生理表型。生理性心脏生长伴随着协调的血管生成反应，在肥厚期间使心肌灌注正常化，最近的研究支持 TH 及其内皮细胞表面整合素受体和核受体在 TH 诱导的肥厚期间的新生血管形成中发挥重要作用。本综述探讨了甲状腺激素诱导的心肌肥厚中激活的这些分子机制和细胞内信号通路，这些机制和信号通路支持其在治疗心脏病方面的治疗潜力。
