Cardiac lipoprotein lipase activity in the hypertrophied heart may be regulated by fatty acid flux

Hui‐Kang, David; Caldwell, Germaine

doi:10.1016/j.bbalip.2011.12.004

Cited by 14 publications

(13 citation statements)

References 44 publications

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“…Angptl4 is implicated in the regulation of glucose homeostasis, insulin sensitivity, and lipid metabolism (7) and is associated with angiogenesis-related disorders, such as cardiovascular diseases (cardiac hypertrophy and atherosclerosis) (8)(9)(10)(11)(12), ischemia (4,13), tumor growth (4,14,15), diabetes (16,17), wound healing (18,19), and inflammation (5). Angptl4 is also believed to play a role in the regulation of airway remodeling in asthma and chronic obstructive pulmonary disease (20,21).…”

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confidence: 99%

Acute-Phase Protein α1-Antitrypsin—A Novel Regulator of Angiopoietin-like Protein 4 Transcription and Secretion

Frenzel

Wrenger

Immenschuh

et al. 2014

The Journal of Immunology

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The angiopoietin-like protein 4 (angptl4, also known as peroxisome proliferator–activated receptor [PPAR]γ–induced angiopoietin-related protein) is a multifunctional protein associated with acute-phase response. The mechanisms accounting for the increase in angptl4 expression are largely unknown. This study shows that human α1-antitrypsin (A1AT) upregulates expression and release of angplt4 in human blood adherent mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2- to 174-fold, respectively, relative to controls. In endothelial cells, the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml A1AT (11-fold induction versus controls). In 10 emphysema patients receiving A1AT therapy (Prolastin), plasma angptl4 levels were higher relative to patients without therapy (nanograms per milliliter, mean [95% confidence interval] 127.1 [99.5–154.6] versus 76.8 [54.8–98.8], respectively, p = 0.045) and correlated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pretreated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of HIF-1α, an upregulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute-phase protein A1AT is a physiological regulator of angptl4, another acute-phase protein.

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confidence: 99%

Acute-Phase Protein α1-Antitrypsin—A Novel Regulator of Angiopoietin-like Protein 4 Transcription and Secretion

Frenzel

Wrenger

Immenschuh

et al. 2014

The Journal of Immunology

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“…Loss of angptl-4 is associated with decreased plasma TAG through increased LPL-mediated clearance, whilst increased angptl-4 expression is associated with inhibited H-LPL and increased plasma TAG, together with cardiac dysfunction [74]. A similar mechanism has also been noted following high-fat feeding, which increases angptl-4 [58], suggesting a mechanism of cardiac LPL regulation in situ related to TAG-FA flux. However, chronic intermittent hypoxia has no effect on H-LPL activity or cardiac TAG uptake, despite inhibiting adipose LPL through upregulating angptl-4 [13].…”

Section: Lipoprotein Lipase Mediated Myocardial Tag Uptakementioning

confidence: 65%

“…It is likely that there is constitutive enzyme expression, perhaps reflecting the availability of VLDL-TAG regardless of nutritional status. Plasma TAG may modulate LPL and hence cardiac TAG assimilation [58,68], and TGRLPs modified heparin-releasable H-LPL activity [16]. Other…”

Section: Lipoprotein Lipase Mediated Myocardial Tag Uptakementioning

confidence: 99%

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The role of triacylglycerol in cardiac energy provision

Evans

Hui‐Kang

2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Triacylglycerols (TAG) constitute the main energy storage resource in mammals, by virtue of their high energy density. This in turn is a function of their highly reduced state and hydrophobicity.Limited water solubility, however, imposes specific requirements for delivery and uptake mechanisms on TAG-utilising tissues, including the heart, as well as intracellular disposition. TAGs constitute potentially the major energy supply for working myocardium, both through bloodborne provision and as intracellular TAG within lipid droplets, but also provide the heart with fatty acids (FA) which the myocardium cannot itself synthesise but are required for glycerolipid derivatives with (non-energetic) functions, including membrane phospholipids and lipid signalling molecules. Furthermore they serve to buffer potentially toxic amphipathic fatty acid derivatives.Intracellular handling and disposition of TAGs and their FA and glycerolipid derivatives similarly requires dedicated mechanisms in view of their hydrophobic character. Dysregulation of utilisation can result in inadequate energy provision, accumulation of TAG and/or esterified species, and these may be responsible for significant cardiac dysfunction in a variety of disease states. This review will focus on the role of TAG in myocardial energy provision, by providing FAs from exogenous and endogenous TAG sources for mitochondrial oxidation and ATP production, and how this can change in disease and impact on cardiac function. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 3Key words:heart; triacylglycerol; very-low-density lipoprotein; VLDL; chylomicron; lipid droplet Highlights: Triacylglycerols are supplied to the myocardium within chylomicrons and VLDL  Heart assimilates triacylglycerol-rich lipoproteins by LPL and receptor-mediated routes  Exogenous triacylglycerol-derived fatty acids enter an intracellular lipid pool  Intracardiac triacylglycerol is an important source of fatty acids for oxidation  Dysregulation of triacylglycerol metabolism is associated with cardiac dysfunction

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“…Briefly, anaesthesia was induced with isofluorane (4% v/v in oxygen) and following thoracotomy, hearts, excised with lungs and thymus in situ, were immersed in ice-cold Krebs-Hensleit medium, which contained the following (in mmoll -1 ): NaCl (120), KCl (4.8), NaHCO 3 (25), MgSO 4 ·7H 2 O (1.2), KH 2 PO 4 (1.2), glucose (10) and CaCl 2 (1.3), gassed with oxygen/CO 2 (95:5). The aorta was cannulated (16G cannula), and then perfused in retrograde fashion by the method of Langendorff, with modifications (Hauton and Caldwell, 2012). Hearts were maintained at either 25 or 37°C and perfused at a constant pressure (100cm H 2 O).…”

Section: Ex Vivo Cardiac Performancementioning

confidence: 99%

Is cold acclimation of benefit to hibernating rodents?

Egginton

May

Deveci

et al. 2013

Journal of Experimental Biology

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SUMMARYThe thermal challenge associated with cold acclimation (CA) and hibernation requires effective cardio-respiratory function over a large range of temperatures. We examined the impact of acute cooling in a cold-naïve hibernator to quantify the presumed improvement in cardio-respiratory dysfunction triggered by CA, and estimate the role of the autonomic nervous system in optimising cardiac and respiratory function. Golden hamsters (Mesocricetus auratus) were held at a 12h:12h light:dark photoperiod and room temperature (21°C euthermic control) or exposed to simulated onset of winter in an environmental chamber, by progression to 1h:23h light:dark and 4°C over 4weeks. In vivo acute cooling (core temperature T b =25°C) in euthermic controls led to a hypotension and bradycardia, but preserved cardiac output. CA induced a hypertension at normothermia (T b =37°C) but on cooling led to decreases in diastolic pressure below euthermic controls and a decrease in cardiac output, despite an increase in left ventricular conductance. Power spectral analysis of heart rate variability suggested a decline in vagal tone on cooling euthermic hamsters (T b =25°C). Following CA, vagal tone was increased at T b =37°C, but declined more quickly on cooling (T b =25°C) to preserve vagal tone at levels similar to euthermic controls at T b =37°C. For the isolated heart, CA led to concentric hypertrophy with decreased end-diastolic volume, but with no change in intrinsic heart rate at either 37 or 25°C. Mechanical impairment was noted at 37°C following CA, with peak developed pressure decreased by 50% and peak rate-pressure product decreased by 65%; this difference was preserved at 25°C. For euthermic hearts, coronary flow showed thermal sensitivity, decreasing by 65% on cooling (T=25°C). By contrast, CA hearts had low coronary flow compared with euthermic controls, but with a loss of thermal sensitivity. Together, these observations suggest that CA induced a functional impairment in the myocardium that limits performance of the cardiovascular system at euthermia, despite increased autonomic input to preserve cardiac function. On acute cooling this autonomic control was lost and cardiac performance declined further than for cold-naïve hamsters, suggesting that CA may compromise elements of cardiovascular function to facilitate preservation of those more critical for subsequent rewarming. Supplementary material available online at

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Cardiac lipoprotein lipase activity in the hypertrophied heart may be regulated by fatty acid flux

Cited by 14 publications

References 44 publications

Acute-Phase Protein α1-Antitrypsin—A Novel Regulator of Angiopoietin-like Protein 4 Transcription and Secretion

Acute-Phase Protein α1-Antitrypsin—A Novel Regulator of Angiopoietin-like Protein 4 Transcription and Secretion

The role of triacylglycerol in cardiac energy provision

Is cold acclimation of benefit to hibernating rodents?

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