Right ventricular pressure overload alters cardiac lipid composition

Koop, A M C; Hagdorn, Quint A.J.; Bossers, Guido P L; Leusden, Tom van; Gerding, A. M.; Weeghel, Michel van; Vaz, Frédéric M.; Koonen, Debby P. Y.; Silljé, Herman H W; Berger, Rudolphus; Bartelds, Beatrijs

doi:10.1016/j.ijcard.2019.04.004

Cited by 10 publications

(7 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both ventricles demonstrated a strong increase in NPPA expression, but the increase in NPPA expression was most abundant in the RV, in agreement with the most pronounced dysfunction of the RV, compared to the LV. Levels of ATP remained unaltered in the RV, and thus challenge the 'engine out of fuel' concept (Neubauer, 2007), as has also been done recently in the pressure-loaded RV (Koop et al, 2019). RV adaptation further comprises increased RCAN1 expression, MHC isoform switch and increased pERK1/2 protein expression, indicative of calcineurin activation and a stressrelated hypertrophic response (Mercadier et al, 1981;Wilkins et al, 2004).…”

Section: Discussionmentioning

confidence: 67%

Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis

et al. 2021

View full text Add to dashboard Cite

BackgroundRight ventricular (RV) function and failure are key determinants of morbidity and mortality in various cardiovascular diseases. Myocardial fibrosis is regarded as a contributing factor to heart failure, but its importance in RV failure has been challenged. This study aims to assess whether myocardial fibrosis drives the transition from compensated to decompensated volume load-induced RV dysfunction.MethodsWistar rats were subjected to aorto-caval shunt (ACS, n = 23) or sham (control, n = 15) surgery, and sacrificed after 1 month, 3 months, or 6 months. Echocardiography, RV pressure-volume analysis, assessment of gene expression and cardiac histology were performed.ResultsAt 6 months, 6/8 ACS-rats (75%) showed clinical signs of RV failure (pleural effusion, ascites and/or liver edema), whereas at 1 month and 3 months, no signs of RV failure had developed yet. Cardiac output has increased two- to threefold and biventricular dilatation occurred, while LV ejection fraction gradually decreased. At 1 month and 3 months, RV end-systolic elastance (Ees) remained unaltered, but at 6 months, RV Ees had decreased substantially. In the RV, no oxidative stress, inflammation, pro-fibrotic signaling (TGFβ1 and pSMAD2/3), or fibrosis were present at any time point.ConclusionsIn the ACS rat model, long-term volume load was initially well tolerated at 1 month and 3 months, but induced overt clinical signs of end-stage RV failure at 6 months. However, no myocardial fibrosis or increased pro-fibrotic signaling had developed. These findings indicate that myocardial fibrosis is not involved in the transition from compensated to decompensated RV dysfunction in this model.

show abstract

Section: Discussionmentioning

confidence: 67%

Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The amount of CL and its FA composition (mainly C18:2 content) are altered in various pathological human and animal models of heart failure, ischemia/reperfusion injury, and diabetic cardiomyopathy [ 45 , 46 , 47 ]. These alterations are also observed in both left and right ventricular diseases [ 48 ]. The symmetry of CL is lost if it contains at least one different FA residue or oxidative modification, and such an asymmetric CL is involved as a precursor signaling molecule [ 40 ].…”

Section: Fas Control the Heart As A Component Of Membrane Phospholipidsmentioning

confidence: 99%

Qualitative and Quantitative Effects of Fatty Acids Involved in Heart Diseases

et al. 2022

View full text Add to dashboard Cite

Fatty acids (FAs) have structural and functional diversity. FAs in the heart are closely associated with cardiac function, and their qualitative or quantitative abnormalities lead to the onset and progression of cardiac disease. FAs are important as an energy substrate for the heart, but when in excess, they exhibit cardio-lipotoxicity that causes cardiac dysfunction or heart failure with preserved ejection fraction. FAs also play a role as part of phospholipids that compose cell membranes, and the changes in mitochondrial phospholipid cardiolipin and the FA composition of plasma membrane phospholipids affect cardiomyocyte survival. In addition, FA metabolites exert a wide variety of bioactivities in the heart as lipid mediators. Recent advances in measurement using mass spectrometry have identified trace amounts of n-3 polyunsaturated fatty acids (PUFAs)-derived bioactive metabolites associated with heart disease. n-3 PUFAs have a variety of cardioprotective effects and have been shown in clinical trials to be effective in cardiovascular diseases, including heart failure. This review outlines the contributions of FAs to cardiac function and pathogenesis of heart diseases from the perspective of three major roles and proposes therapeutic applications and new medical perspectives of FAs represented by n-3 PUFAs.

show abstract

“…Data from recent studies imply that RV inability to modify substrate flux contributes to energy imbalance and results in contractile failure after acute RVPO. Some data suggest that chronic RVPO promotes metabolic changes which lead to maladaptive hypertrophy in the RV (Koop et al, 2019; Piao et al, 2010; Prisco et al, 2022; Sheikh et al, 2009). Furthermore, reversal of these metabolic perturbations, which include alterations in substrate utilization, prevents or limits functional decompensation.…”

Section: Introductionmentioning

confidence: 99%

Right ventricular energy metabolism in a porcine model of acute right ventricular pressure overload after weaning from cardiopulmonary bypass

Kajimoto¹,

Nuri

Sleasman

et al. 2022

Physiological Reports

View full text Add to dashboard Cite

Acute right ventricular pressure overload (RVPO) occurs following congenital heart surgery and often results in low cardiac output syndrome. We tested the hypothesis that the RV exhibits limited ability to modify substrate utilization in response to increasing energy requirements during acute RVPO after cardiopulmonary bypass (CPB). We assessed the RV fractional contributions (Fc) of substrates to the citric acid cycle in juvenile pigs exposed to acute RVPO by pulmonary artery banding (PAB) and CPB. Sixteen Yorkshire male pigs (median 38 days old, 12.2 kg of body weight) were randomized to SHAM (Ctrl, n = 5), 2‐h CPB (CPB, n = 5) or CPB with PAB (PAB‐CPB, n = 6). Carbon‐13 (13C)‐labeled lactate, medium‐chain, and mixed long‐chain fatty acids (MCFA and LCFAs) were infused as metabolic tracers for energy substrates. After weaning from CPB, RV systolic pressure (RVSP) doubled baseline in PAB‐CPB while piglets in CPB group maintained normal RVSP. Fc‐LCFAs decreased significantly in order PAB‐CPB > CPB > Ctrl groups by 13C‐NMR. Fc‐lactate and Fc‐MCFA were similar among the three groups. Intragroup analysis for PAB‐CPB showed that the limited Fc‐LCFAs appeared prominently in piglets exposed to high RVSP‐to‐left ventricular systolic pressure ratio and high RV rate‐pressure product, an indicator of myocardial oxygen demand. Acute RVPO after CPB strongly inhibits LCFA oxidation without compensation by lactate oxidation, resulting in energy deficiency as determined by lower (phosphocreatine)/(adenosine triphosphate) in PAB‐CPB. Adequate energy supply but also metabolic interventions may be required to circumvent these RV energy metabolic abnormalities during RVPO after CPB.

show abstract

Right ventricular pressure overload alters cardiac lipid composition

Cited by 10 publications

References 69 publications

Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis

Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis

Qualitative and Quantitative Effects of Fatty Acids Involved in Heart Diseases

Right ventricular energy metabolism in a porcine model of acute right ventricular pressure overload after weaning from cardiopulmonary bypass

Contact Info

Product

Resources

About