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Koop 2018 11th Internat Confer Neonat Childh Pulmon Vasc Dis

From Bioblast
Decrease of polyunsaturated fatty acids in right ventricular dysfunction due to pressure overload.

Link: [1]

Koop A, Hagdorn Q, Bossers G, van Leusden T, Gerding A, van Weeghel M, Vaz F, Koonen D, Sillje H, Berger R, Bartelds B (2018)

Event: 11th Internat Confer Neonat Childh Pulmon Vasc Dis

Right ventricular (RV) failure due to pressure load is an important determinant of clinical outcome in pulmonary hypertension (PH). Recently, changes in ventricular lipid content has been suggested as potential inducer of pediatric heart failure. In the present experimental rat study, we aimed to obtain insight in temporal changes in RV function, remodeling, and metabolism due to increased RV afterload, with specific focus on RV lipid content.

Wistar rats were subjected to pulmonary artery banding (PAB; nโ€‰=โ€‰25) or sham surgery (nโ€‰=โ€‰14). Hemodynamic parameters were derived with echocardiography, whereas cellular and metabolic assessments took place using quantitative polymerase chain reaction (qPCR), stainings, and Oroboros at 2, 5, and 12 weeks. Lipidomic analysis was performed at 12 weeks of pressure load.

In this model, early RV dysfunction and progressive RV remodeling occurred without clinical failure. After 12 weeks of pressure load, lipidomics revealed significant decreases of myocardial diglyceride and cardiolipin species; triglyceride also tended to be decreased. These decreases were driven by the downregulation of polyunsaturated fatty acids, including the abundant form tetralinoleylcardiolipin. Changes in intracardiac lipid profile were accompanied with an increase in carbohydrate metabolism without changes in mitochondrial fatty acid metabolism. This altered the balance between fatty acid carbohydrate metabolism in favor of the latter.

We conclude that RV dysfunction due to PAB is associated with decreased RV lipid content, characterized by a decrease of polyunsaturated lipids, including tetralinoeylcardiolipin, in the absence of clinical failure. The present study suggests that altered intra-cardiac lipid composition precedes and contributes to the development of RV failure.

โ€ข Bioblast editor: Kandolf G โ€ข O2k-Network Lab: NL Groningen Reijngoud RJ

Labels: MiParea: Respiration  Pathology: Cardiovascular 

Organism: Rat  Tissue;cell: Heart 

HRR: Oxygraph-2k 



Univ Medical Center Groningen, The Netherlands; Univ Amsterdam, The Netherlands