scholarly journals DIFFERENTIAL BIOENERGETICS IN ADULT RAT CARDIOMYOCYTES ISOLATED FROM THE RIGHT VERSUS LEFT VENTRICLE

2020 ◽  
Author(s):  
Quyen L. Nguyen ◽  
Krithika Rao ◽  
Steven J. Mullett ◽  
Stacy G. Wendell ◽  
Claudette St. Croix ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Left Ventricle ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Function ◽  
Left Ventricular ◽  
Acid Oxidation ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
The Right ◽  
Transport Complex

ABSTRACTThe right and left ventricle of the heart have distinctly different developmental origins and are affected differently by similar pathological stimuli. Though it is well established that the heart relies almost entirely on mitochondrial function to sustain energy production, it remains unclear whether bioenergetics differ in the two ventricles. Herein, we define a novel methodology to optimize the isolation of intact cardiomyocytes from the right versus the left ventricle. We demonstrate that this segmental Langendorff-free methodology yields viable cardiomyocytes with intact mitochondrial function. Further, we compare bioenergetics in right versus left ventricle cardiomyocytes and show that cardiomyocytes from the right ventricle have a greater maximal capacity for respiration and enhanced glycolytic rate. This increase in respiration was concomitant with increased fatty acid oxidation and levels of fatty acid oxidation proteins, but no change in mitochondrial electron transport complex expression. These data validate a potentially powerful tool to evaluate differences in right and left ventricular function and advance the understanding of cardiac bioenergetic differences. These data will be discussed in the context of differential responses by the right versus ventricle in pathology.

scholarly journals PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis

2017 ◽  
Vol 312 (2) ◽  
pp. H239-H249 ◽  
Author(s):  
Stephen W. Standage ◽  
Brock G. Bennion ◽  
Taft O. Knowles ◽  
Dolena R. Ledee ◽  
Michael A. Portman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Mouse Models ◽  
Heart Function ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Regulatory State ◽  
Peroxisome Proliferator Activated Receptor

Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild-type (WT) mice over the first 24 h of sepsis, but that mice lacking PPARα ( Ppara−/−) cannot sustain the elevated heart function necessary to compensate for sepsis pathophysiology. Left ventricular shortening fraction, measured 24 h after initiation of sepsis by echocardiography, was higher in WT mice than in Ppara−/− mice. Ex vivo working heart studies demonstrated greater developed pressure, contractility, and aortic outflow in WT compared with Ppara−/− mice. Furthermore, cardiac fatty acid oxidation was increased in WT but not in Ppara−/− mice. Regulatory pathways controlling pyruvate incorporation into the citric acid cycle were inhibited by sepsis in both genotypes, but the regulatory state of enzymes controlling fatty acid oxidation appeared to be permissive in WT mice only. Mitochondrial ultrastructure was not altered in either genotype indicating that severe mitochondrial dysfunction is unlikely at this stage of sepsis. These data suggest that PPARα expression supports the hyperdynamic cardiac response early in the course of sepsis and that increased fatty acid oxidation may prevent morbidity and mortality. NEW & NOTEWORTHY In contrast to previous studies in septic shock using experimental mouse models, we are the first to demonstrate that heart function increases early in sepsis with an associated augmentation of cardiac fatty acid oxidation. Absence of peroxisome proliferator-activated receptor-α (PPARα) results in reduced cardiac performance and fatty acid oxidation in sepsis.

Chronic inhibition of fatty acid oxidation: new model of diastolic dysfunction

1990 ◽  
Vol 258 (1) ◽  
pp. H51-H56 ◽  
Author(s):  
S. E. Litwin ◽  
T. E. Raya ◽  
R. G. Gay ◽  
J. B. Bedotto ◽  
J. J. Bahl ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Chain Fatty Acid ◽  
Acid Oxidation ◽  
Long Chain Fatty Acid ◽  
Ventricular Relaxation ◽  
Left Ventricular Chamber ◽  
Long Chain

This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mg.kg-1.day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65%, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increased, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.

Abstract 169: miR-21-5p Regulation of Lipid Content and Peroxidation in H9C2 Cells

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sandra Chuppa ◽  
Alison J Kriegel
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Content ◽  
Untreated Control ◽  
Left Ventricular ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
H9c2 Cells

Cardiovascular pathologies are the leading single cause of death in chronic kidney disease (CKD) patients. We have found that the 5/6 nephrectomy model of CKD leads to an upregulation of miR-21-5p in the left ventricle 7 weeks after surgery, targeting peroxisome proliferator-activated receptor alpha (PPARα). PPARα is a regulator of fatty acid uptake and metabolism. In our model we find that suppression of miR-21-5p alters the expression of numerous genes involved with fatty acid oxidation and glycolysis, presumably through its regulatory action on PPARα and/or additional targets. We also find that 5/6Nx rats exhibit dyslipidemia and increased left ventricular lipid content at this time. In this study we evaluated the potential for knockdown or overexpression of miR-21-5p to regulate lipid content and peroxidation in H9C2 cells. Cells were transfected with anti-miR-21-5p (40nM), pre-miR-21-5p (20nM) or appropriate scrambled oligonucleotide controls. After 24 hours medium was changed and half of the cells from each transfection group were treated with lipid (0.66 mM oleic acid and 0.33 mM palmitic acid) for 48 hours (n=6/treatment group for each set of experiments). Lipid content, measured by AdipoRed assay (Lonza) was significantly increased with lipid treatment (nearly two-fold). Overexpression of miR-21-5p significantly attenuated this increase (228.0 ± 9.7 vs. 198.2 ± 8.9% of untreated control), while suppression of miR-21-5p augmented lipid content (235.8 ± 11.2 vs. 328.1 ± 12.3% of untreated control). These results were supported by imaging of Oil Red O stained cells. We found that the abundance of malondialdehyde (MDA), a product of lipid peroxidation, was significantly increased in response to lipid treatment. Overexpression of miR-21-5p reduced MDA content in untreated and lipid treated cells, suggesting that miR-21-5p reduces oxidative stress. Suppression of miR-21-5p had no effect on MDA levels. These results indicate that overexpression of miR-21-5p attenuates both lipid content and lipid peroxidation in H9C2 cells. Ongoing studies aimed at evaluation of alterations in fatty acid oxidation and oxidative stress will further aid in determining the functional impact of miR-21-5p on associated pathways in cardiac tissue.

Changes in esterified fatty acids in the isolated, perfused rabbit heart

1968 ◽  
Vol 46 (10) ◽  
pp. 1241-1246 ◽  
Author(s):  
K. Kako ◽  
M. J. G. Dubuc
Keyword(s):  
Fatty Acid ◽  
Left Ventricle ◽  
Neutral Lipid ◽  
Lipid Fraction ◽  
Fatty Acid Distribution ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Buffer Solution ◽  
The Right ◽  
Lipid Stores

The hearts of fasted (48 h) or fed rabbits were perfused with buffer solution with or without glucose. The right ventricle was removed at the 10th min of perfusion. The left ventricle was perfused for 10, 70, or 130 min. Cardiac lipids were analyzed by the hydroxamic acid method and gas chromatography. The neutral lipid fraction from the heart of the fasted rabbit contained relatively more linoleic and less palmitic acid than that from the heart of the fed animal. Similarly, relatively more oleic and less stearic acids were found in the phospholipid fraction from the heart of the fasted rabbit. There was a slight difference in fatty acid distribution between the right and left ventricular lipids at the 10th min of perfusion.The left ventricle of the fasted rabbit lost two-thirds of its neutral lipid stores during perfusion for 120 min with a substrate-free medium. Some of the phospholipid also disappeared between the 70th and the 130th min of perfusion. No measurable loss of lipids was found in the hearts of fed animals perfused under the same conditions. In the presence of glucose in the perfusing medium, cardiac lipid contents remained unchanged during perfusion regardless of the nutritional state of the animal. Esterified fatty acid composition did not change significantly during perfusion. The significance of these observations is discussed in relation to possible metabolic control systems in fasted and fed animals.

Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, improves left ventricular function in dogs with chronic heart failure

2002 ◽  
Vol 8 (6) ◽  
pp. 416-422 ◽  
Author(s):  
Hani N. Sabbah ◽  
Margaret P. Chandler ◽  
Takayuki Mishima ◽  
George Suzuki ◽  
Pervaiz Chaudhry ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Chronic Heart Failure ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Fatty Acid Oxidation ◽  
Left Ventricular ◽  
Acid Oxidation

Abstract 082: Deletion of Mitochondrial Aldehyde Dehydrogenase 2 Restrains Cardiac Fatty Acid Oxidation during Pressure-Overload Induced Heart Failure

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Fan Fan ◽  
Aijun Sun ◽  
Guang Xia ◽  
Yunzeng Zou ◽  
Kai Hu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Aldehyde Dehydrogenase ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Acid Oxidation ◽  
Base Line ◽  
Aldehyde Dehydrogenase 2 ◽  
Metabolic Remodeling

Rationale: Mitochondrial Aldehyde dehydrogenase 2 (ALDH2) is regarded as an inner protector of cardiac diseases, which downregulation has been reported to induce cardiac metabolic remodeling and augmented glucose uptake. However, it has not been investigated whether myocardial fatty acid oxidation (FAO) could be regulated by ALDH2. Objective: We hypothesized that global deletion of ALDH2 would deteriorate heart function and energy generation, inhibit cardiac FAO and promote the development of pressure-overload induced heart failure. Methods and Results: ALDH2 knockout (ALDH2-/-) did not led to considerable birth defects and cardiac dysfunction in base line. Pressure overload were induced by transverse aortic constriction (TAC) for 4weeks. In echocardiographic and hemodynamic test, left ventricular systolic functions were decreased in ALDH2-/- TAC mice compared with wild type (WT) TAC mice. Myocardial morphology and subcellular structure examinations shown ALDH2-/- TAC mice exhibited cardiac hypertrophy with a significant mitochondrial destroy relative to WT-TAC. Meanwhile, a decreased FAO and ATP production were detected (54±3.6% and 77±1.5%, p<0.05,respectively) in ALDH2-/- sham myocardium, which were aggravated by pressure overload. Therefore, ALDH2 deletion accelerated cardiac energy remolding. Furthermore, ALDH2-/- repressed AMP-activated protein kinase (AMPK) phosphorylation(49±4.6%, p<0.05) and subsequently inhibited the activation of peroxisome proliferator-activated receptor a (PPARa) (31±2.9%, p<0.05) - carnitine palmitoyl transferase 1 (CPT1) (81.5±5.2%, p<0.05) - fatty acid transportation pathway, which induced inefficient of FAO. Conclusions: These data of present study suggest that ALDH2 deficiency promotes heart failure and cardiac metabolic remodeling by inhibiting myocardial FAO through AMPK-PPARa-CPT1 pathway.

57 THE EFFECTS OF INCREASED EXPRESSION OF FATTY ACID OXIDATION ENZYMES ON LEFT VENTRICULAR MASS AND FUNCTION IN HEART FAILURE:

2005 ◽  
Vol 53 (2) ◽  
pp. S366.3-S366
Author(s):  
E. E. Morgan ◽  
T. A. McElfresh ◽  
M. P. Chandler ◽  
M. E. Young ◽  
W. C. Stanley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Left Ventricular Mass ◽  
Fatty Acid Oxidation ◽  
Left Ventricular ◽  
Acid Oxidation ◽  
Ventricular Mass ◽  
And Function
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