Changes in Cardiac Substrate Transporters and Metabolic Proteins Mirror the Metabolic Shift in Patients with Aortic Stenosis

Heather, Lisa C.; Howell, Neil; Emmanuel, Yaso; Cole, Mark A.; Frenneaux, Michael; Pagano, Domenico; Clarke, Kieran

doi:10.1371/journal.pone.0026326

Cited by 35 publications

(28 citation statements)

References 34 publications

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“…The level of CD36 expression in the failing heart is not well characterized. The transition in substrate utilization away from LCFA is mirrored by changes in substrate transporter expression in human studies ( 47 ), and a similar relationship was found in failing rat hearts following myocardial infarction ( 48 ). The spontaneously hypertensive rat (SHR) continues to express CD36; however, there are mutations in the gene and the protein undergoes less posttranslational modifi cation ( 39 ).…”

Section: Fractional Contribution Of Exogenous Lcfa To Acetyl Coa Formmentioning

confidence: 83%

Multiphasic triacylglycerol dynamics in the intact heart during acute in vivo overexpression of CD36

Carley

Wang

et al. 2013

Journal of Lipid Research

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The specifi c kinetic characteristics of intramyocellular triacylglycerol (TAG) turnover, involving synthesis and lipolysis in the intact beating heart, have been largely uncharacterized to date, and the mechanisms linking uptake and storage dynamics have until now remained elusive. This work examines the dynamics of the TAG pool in the intact heart, under normal conditions and in response to acute changes in in vivo, transporter protein-mediated lipid uptake, in the absence of developmental adaptations that might otherwise occur in a murine mouse model. Through the use of dynamic mode 13 CNMR and endpoint enrichment analysis via LC/MS, we have been able to quantify the turnover of LCFA in and out of the TAG pool and identify distinct exponential and linear characteristics that are associated with regulatory processes of lipid dynamics in the cell ( 1-3 ).TAG is the major source of energy stores within the heart. Traditionally viewed as an inert pool of unmetabolized long chain fatty acids, the newer, emerging realization is that TAG content in the cardiomyocyte is a dynamic metabolic pool that supports the high demand for fatty acid oxidation by the heart, as well as contributes fatty acids that serve as ligands for nuclear receptors and the induction of nuclear transcription factor activity ( 1, 2, 4, 5 ). Additionally, the rates of TAG turnover and content serve as neutral buffers implicated in limiting the formation and accumulation of physiological active and potentially toxic acyl intermediates and derivatives ( 6, 7 ). TAG turnover responds to the magnitude of lipid pool; TAG turnover increases following high-fat diet ( 1 ) in diabetes ( 3 ) or in mouse models of increased lipid mobilization, such as the peroxisome proliferator-activated receptor (PPAR) ␣ or peroxisome Abstract Cardiac triacylglycerol (TAG) stores buffer the intracellular availability of long chain fatty acid (LCFA) that act as nuclear receptor ligands, substrate for lipotoxic derivatives, and high energy-yield fuel. The kinetic characteristics of TAG turnover and homeostatic mechanisms linking uptake and storage dynamics in hearts have until now remained elusive. This work examines TAG pool dynamics in the intact beating heart, under normal conditions and in response to acute gene expression-induced changes in CD36. Dynamic mode 13 C NMR elucidated multiple kinetic processes in 13 C-palmitate incorporation into TAG: an initial, saturable exponential component and a slower linear rate. Although previous work indicates the linear component to refl ect TAG turnover, we hypothesized the saturable exponential to refl ect transport of LCFA across the sarcolemma. Thus, we overexpressed the LCFA transporter CD36 through cardiac-specifi c adenoviral infection in vivo. Within 72 h, CD36 expression was increased 40% in intact hearts, accelerating the exponential phase relative to PBS-infused hearts. TAG turnover also increased with elevations in adipose triglyceride lipase (ATGL) and a modest increase in diacylglycerol acyltransferase 1 (DGAT1), wi...

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Section: Fractional Contribution Of Exogenous Lcfa To Acetyl Coa Formmentioning

confidence: 83%

Multiphasic triacylglycerol dynamics in the intact heart during acute in vivo overexpression of CD36

Carley

Wang

et al. 2013

Journal of Lipid Research

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“…In the hypertrophied heart a greater proportion of the energy is derived from glucose. 116,117 Analyses of tissue from patients undergoing SAVR have shown that the abundance of the glucose transporter GLUT4 relative to the fatty acid transporter FAT/CD36 correlated with severity of LV hypertrophy. 117 Micro RNA (miRNA) as a potential biomarker in AS miRNA is small RNA that regulates gene expression by targeting mRNA for cleavage or translational repression.…”

Section: Markers Of Alteration In Cardiac Metabolismmentioning

confidence: 99%

“…116,117 Analyses of tissue from patients undergoing SAVR have shown that the abundance of the glucose transporter GLUT4 relative to the fatty acid transporter FAT/CD36 correlated with severity of LV hypertrophy. 117 Micro RNA (miRNA) as a potential biomarker in AS miRNA is small RNA that regulates gene expression by targeting mRNA for cleavage or translational repression. 118,119 These 19-25 nucleotide long non-coding RNA could function as "on/off switches" for various cellular functions and processes.…”

Section: Markers Of Alteration In Cardiac Metabolismmentioning

confidence: 99%

Biomarkers in Aortic Stenosis: A Systematic Review

et al. 2017

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Aortic stenosis (AS) is one of the most common heart valve diseases among adults. When symptoms develop alongside severe AS, there is a poor prognosis unless aortic valve replacement (AVR) is performed; however, many patients do not report symptoms even when AS is severe. The optimal timing of AVR for these patients remains uncertain and controversial. AS is a heterogeneous disease with a complex pathophysiology involving structural and biological changes of the valve as well as adaptive and maladaptive compensatory changes in the myocardium and vasculature in response to chronic pressure overload. Several biomarkers reflecting these processes have been identified and have shown to have utility in predicting symptom onset and clinical events before and after AVR. Herein we systematically review biomarkers that have been studied in the setting of AS and summarize their potential use for risk stratification and ultimately to guide the optimal timing of AVR.

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“…To date, abnormalities in several processes of fatty acid metabolism have been identified in patients with heart failure. This includes selection [19], transport [20][21], oxidation [20][21][22] and respiratory chain activity [20][21][23][24][25][26]. Free FAs cross the lipid bilayer in a passive manner via flip-flop or by using transport proteins (i.e.…”

Section: Cardiac Energetics -An Engine Out Of Fuelmentioning

confidence: 99%

Metabolomics — A wide-open door to personalized treatment in chronic heart failure?

Marcinkiewicz-Siemion

Ciborowski

Krętowski

et al. 2016

International Journal of Cardiology

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Changes in Cardiac Substrate Transporters and Metabolic Proteins Mirror the Metabolic Shift in Patients with Aortic Stenosis

Cited by 35 publications

References 34 publications

Multiphasic triacylglycerol dynamics in the intact heart during acute in vivo overexpression of CD36

Multiphasic triacylglycerol dynamics in the intact heart during acute in vivo overexpression of CD36

Biomarkers in Aortic Stenosis: A Systematic Review

Metabolomics — A wide-open door to personalized treatment in chronic heart failure?

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