IGF1-PI3K-induced physiological cardiac hypertrophy: Implications for new heart failure therapies, biomarkers, and predicting cardiotoxicity.
IGF1-PI3K-induced physiological cardiac hypertrophy: Implications for new heart failure therapies, biomarkers, and predicting cardiotoxicity.
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DOI：
10.1016/j.jshs.2020.11.009
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发表时间：
2021-12
影响因子：
11.7
通讯作者：
McMullen JR
中科院分区：
文献类型：
--
作者：
Bass-Stringer S;Tai CMK;McMullen JR
IGF1-PI3K通路介导运动诱导的心脏生长和保护。模仿运动对心脏的好处的策略是非常有趣的。表征心脏PI3K活性改变的动物模型可以识别心脏病的新药物靶点，以及区分健康和患病心脏的生物标志物。增加PI3K活性的治疗可能为改善衰竭心脏的功能提供了一种有希望的方法。降低PI3K活性的全身治疗，如某些癌症药物，可能导致心脏毒性。心衰是多种心血管疾病的终点。它是一个日益加重的健康负担，也是世界范围内导致死亡的主要原因。迄今为止，治疗心力衰竭的治疗方案有限，但运动已被公认为为数不多的安全有效的干预措施之一，可以改善患者的预后。然而，缺乏患者依从性仍然是实施以运动为基础的治疗心力衰竭的一个重大障碍。胰岛素样生长因子1 (IGF1) -磷酸肌肽3激酶（PI3K）通路被认为是介导运动诱导的心脏生长和保护的最关键途径。在这里，我们讨论了调节IGF1-PI3K通路的活性如何可能是开发模仿运动对心脏保护作用的治疗方法的有价值的方法。我们概述了一些正在研究的利用pi3为基础的治疗心力衰竭的有前途的方法。我们讨论了在PI3K活性降低的情况下产生的心脏病理和心脏毒性的影响。最后，我们讨论了心脏健康和疾病动物模型的使用，以及心脏PI3K活性升高或降低的遗传小鼠，以发现新的药物靶点和心血管疾病的生物标志物。
The IGF1–PI3K pathway mediates exercise induced heart growth and protection. Strategies to mimic the benefits of exercise on the heart are of substantial interest. Characterizing animal models of altered cardiac PI3K activity can identify new drug targets for heart disease, and biomarkers which distinguish the healthy and diseased heart. Therapies that increase PI3K activity may provide a promising approach to improve function in the failing heart. Systemic therapies that reduce PI3K activity, such as some cancer agents, may lead to cardiotoxicity. Heart failure represents the end point of a variety of cardiovascular diseases. It is a growing health burden and a leading cause of death worldwide. To date, limited treatment options exist for the treatment of heart failure, but exercise has been well-established as one of the few safe and effective interventions, leading to improved outcomes in patients. However, a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure. The insulin-like growth factor 1 (IGF1)–phosphoinositide 3-kinase (PI3K) pathway has been recognized as perhaps the most critical pathway for mediating exercised-induced heart growth and protection. Here, we discuss how modulating activity of the IGF1–PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart. We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure. We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity. Finally, we discuss the use of animal models of cardiac health and disease, and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.
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影响因子：
3.7
作者：
Ferretti R;Moura EG;Dos Santos VC;Caldeira EJ;Conte M;Matsumura CY;Pertille A;Mosqueira M
通讯作者：
Mosqueira M
影响因子：
5.6
作者：
Ghigo A;Li M
通讯作者：
Li M
DOI：
10.1073/pnas.1206432109
发表时间：
2012-10-23
影响因子：
11.1
作者：
Bernardo, Bianca C.;Gao, Xiao-Ming;McMullen, Julie R.
通讯作者：
McMullen, Julie R.
DOI：
10.4084/mjhid.2012.067
发表时间：
2012
影响因子：
3.2
作者：
Efremov DG;Wiestner A;Laurenti L
通讯作者：
Laurenti L
影响因子：
4.2
作者：
Gao, Guangping;Bish, Lawrence T.;Sweeney, H. Lee
通讯作者：
Sweeney, H. Lee