Right ventricular pressure overload alters cardiac lipid composition
Introduction: 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. Methods and results: 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. Conclusion: 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.
|Keywords||Right ventricular dysfunction, Hypertrophy, Metabolism, Diglyceride, Cardiolipin|
|Persistent URL||dx.doi.org/10.1016/j.ijcard.2019.04.004, hdl.handle.net/1765/116814|
|Journal||International Journal of Cardiology|
Koop, A.M.C., Hagdorn, Q.A.J., Bossers, G.P.L., van Leusden, T., Gerding, A., van Weeghel, M, … Bartelds, B. (2019). Right ventricular pressure overload alters cardiac lipid composition. International Journal of Cardiology, 287, 96–105. doi:10.1016/j.ijcard.2019.04.004