Suzuki Yuichiro J, Shults Nataliia V
Department of Pharmacology and Physiology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC, 20057, USA.
Adv Exp Med Biol. 2017;967:315-323. doi: 10.1007/978-3-319-63245-2_19.
Pulmonary hypertension is a devastating disease without cure. The major cause of death among patients with pulmonary hypertension is right heart failure; however, biology of the right heart is not well understood. This lack of knowledge interferes with developing effective therapeutic strategies to treat these patients. In this chapter, we summarize studies performed in our laboratory that investigated the role of redox signaling in the regulation of the right ventricle (RV), using rat models of experimental pulmonary hypertension and right heart failure. Specifically, this chapter covers the topics of (a) redox regulation of serotonin signaling in the RV, (b) the carbonylation-degradation pathway of signal transduction in RV hypertrophy and (c) oxidative modifications in the RV of the SU5416/ovalbumin model of pulmonary arterial hypertension. These studies revealed that redox regulation in the RV is complex and simply giving lots of antioxidants to patients will unlikely benefit them. Deeper understanding of specific and selective redox mechanisms should shed light on how we can develop therapeutic strategies by modulating redox reactions.
肺动脉高压是一种无法治愈的毁灭性疾病。肺动脉高压患者的主要死因是右心衰竭;然而,右心的生物学机制尚未得到充分了解。这种知识的缺乏阻碍了开发有效的治疗策略来治疗这些患者。在本章中,我们总结了在我们实验室进行的研究,这些研究使用实验性肺动脉高压和右心衰竭的大鼠模型,研究了氧化还原信号在右心室(RV)调节中的作用。具体而言,本章涵盖以下主题:(a)右心室中血清素信号的氧化还原调节,(b)右心室肥大中信号转导的羰基化-降解途径,以及(c)肺动脉高压SU5416/卵清蛋白模型右心室中的氧化修饰。这些研究表明,右心室中的氧化还原调节是复杂的,仅仅给患者大量抗氧化剂不太可能使他们受益。对特定和选择性氧化还原机制的更深入理解应该有助于我们了解如何通过调节氧化还原反应来制定治疗策略。