University of Groningen, University Medical Center Groningen, Center for Congenital Heart Diseases, Department of Pediatric Cardiology Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Center for Congenital Heart Diseases, Department of Pediatric Cardiology Groningen, the Netherlands.
Int J Cardiol. 2019 Jul 15;287:96-105. doi: 10.1016/j.ijcard.2019.04.004. Epub 2019 Apr 8.
Right ventricular (RV) failure due to pressure load is an important determinant of clinical outcome in pulmonary hypertension, congenital heart disease and left ventricular failure. The last decades it has become clear that metabolic dysregulation is associated with the development of RV-failure. However, underlying mechanisms remain to be unraveled. Recently, disruption of intracardiac lipid content has been suggested as potential inducer of RV failure. In the present study, we used a rat model of RV-dysfunction and aimed to obtain insight in temporal changes in RV-function, -remodelling and -metabolism and relate this to RV lipid content.
Male Wistar WU rats were subjected to pulmonary artery banding (n = 25) or sham surgery (n = 14) and cellular, hemodynamic and metabolic assessments took place after 2, 5 and 12 weeks. In this model RV dysfunction and remodelling occurred, including early upregulation of oxidative stress markers. After 12 weeks of pressure load, lipidomics revealed significant decreases of myocardial diglycerides and cardiolipins, driven by (poly-)unsaturated forms. The decrease of cardiolipins was driven by its most abundant form, tetralinoleoylcardiolipin. Mitochondrial capacity for fatty acid oxidation preserved, while the capacity for glucose oxidation increased.
RV dysfunction due to pressure load, is associated with decreased intracardiac unsaturated lipids, especially tetralinoleoylcardiolipin. This was accompanied with preserved mitochondrial capacity regarding fatty acids oxidation, with increased capacity for glucose oxidation, and early activation of oxidative stress. We suggest that early interventions should be directed towards preservation of lipid availability as possible mean in order to prevent RV failure.
由于压力负荷导致的右心室（RV）衰竭是肺动脉高压、先天性心脏病和左心室衰竭临床转归的重要决定因素。过去几十年，人们已经清楚地认识到代谢失调与 RV 衰竭的发生有关。然而，其潜在的机制仍有待阐明。最近，有研究表明，心脏内脂质含量的紊乱可能是 RV 衰竭的潜在诱因。在本研究中，我们使用了 RV 功能障碍大鼠模型，旨在深入了解 RV 功能、重塑和代谢的时间变化，并将其与 RV 脂质含量相关联。
雄性 Wistar WU 大鼠接受肺动脉缩窄术（n = 25）或假手术（n = 14），并在术后 2、5 和 12 周进行细胞、血流动力学和代谢评估。在该模型中，RV 功能和重塑发生，包括氧化应激标志物的早期上调。在压力负荷 12 周后，脂质组学显示心肌二酰基甘油和心磷脂含量显著下降，这主要是由（多）不饱和形式驱动的。心磷脂含量的下降是由其最丰富的形式四油酰基心磷脂驱动的。脂肪酸氧化的线粒体容量保持不变，而葡萄糖氧化的容量增加。
压力负荷导致的 RV 功能障碍与心脏内不饱和脂质的减少有关，特别是四油酰基心磷脂。这伴随着脂肪酸氧化线粒体容量的保持，以及葡萄糖氧化容量的增加和氧化应激的早期激活。我们认为，早期干预应该针对脂质可用性的保护，以防止 RV 衰竭。
