PCSK9 deficiency and heart metabolism

2021 ◽  
Vol 331 ◽  
pp. e15
Author(s):  
L. Da Dalt ◽  
L. Castiglioni ◽  
A. Baragetti ◽  
F. Pellegatta ◽  
M. Svecla ◽  
...  
Keyword(s):  
Heart Metabolism

Abstract 102: Time-of-intake Regulates Glucocorticoid Pharmacology Of Cardiac Bioenergetics

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Mattia Quattrocelli ◽  
Michelle Wintzinger ◽  
Karen Miz
Keyword(s):  
Ex Vivo ◽  
Gene Knockout ◽  
Heart Tissue ◽  
Functional Coupling ◽  
Specific Gene ◽  
Heart Metabolism ◽  
Respiratory Capacity ◽  
Circadian Time ◽  
The Impact ◽  
Mitochondrial Respiratory

Glucocorticoid steroids are circadian regulators of energy balance. However, the specific direct effects of glucocorticoids on heart metabolism remain unresolved. Moreover, the impact of circadian time-of-intake on glucocorticoid pharmacology is still unknown. Here, we investigated whether circadian time of exposure gates the effects of synthetic glucocorticoids on heart bioenergetics. We compared the effects of diurnal versus nocturnal glucocorticoids in heart tissue and mitochondria from wildtype mice, controlling the subjective circadian time of drug injection. To avoid interferences from other tissues, we developed an ex vivo system to interrogate the mitochondrial respiratory capacity rate (state III/state IV) in isolated hearts. We found that diurnal but not nocturnal pulse of the glucocorticoid prednisone increased the mitochondrial respiratory capacity rate in heart. This correlated with circadian-restricted effects on mitochondrial abundance. This was remarkable as it contrasts the circadian fluctuations of endogenous glucocorticoids. Using transgenic mice with inducible cardiac-specific gene knockout, we found that the bioenergetic effects of diurnal-restricted prednisone were dependent on the glucocorticoid receptor and its co-factor Kruppel-like factor 15. Considering the bioenergetic decline that hallmarks the aging heart, we asked whether these circadian-gated effects were applicable to aged mice. We therefore treated 24 months-old mice for 12 weeks with a diurnal-restricted regimen of prednisone. Compared to vehicle, diurnal prednisone increased mitochondrial respiration along with NAD + and ATP content in aged hearts. Moreover, lipidomic profiling of myocardial tissue showed that the vast majority of lipids were downregulated after treatment, including triacylglycerols, suggesting a functional coupling between lipid utilization and mitochondrial oxidation in treated hearts. We also found that diurnal-restricted prednisone rescued bioenergetics and improved function in diabetic hearts from db/db mice. In summary, our data indicate that glucocorticoids regulate cardiac bioenergetics according to circadian-time of intake, supporting a role for chrono-pharmacology in aged and diabetic hearts.

scholarly journals Metabolic and functional cardiac changes at II-type pancreatic diabetes and abdominal adiposity in rats

2003 ◽  
Vol 2 (3) ◽  
pp. 30-36
Author(s):  
M. V. Kolbina ◽  
V. T. Dolgikh ◽  
V. I. Chesnokov
Keyword(s):  
Carbohydrate Metabolism ◽  
Contractile Function ◽  
Negative Inotropic Effect ◽  
Glycated Haemoglobin ◽  
Control Group ◽  
Metabolic Disturbances ◽  
Functional Abnormality ◽  
Heart Metabolism ◽  
Pancreatic Diabetes ◽  
Leading Role

Investigation of pathogenetic correlation of abdominal adisposity and II-type pancreatic diabetes (PD) has been made with the aim to reveal the importance of carbohydrate metabolism disturbances at above said pathology combination in cardiac abnormalities. 30 white alley rats at the age of 8-12 months have been included into the experimental group. Control group has been formed of 30 animals. Used methods of investigation: simulation of II-type PD in rats with streptozotocin and study of carbohydrate metabolism indices in entire organism as well as contractile function indices and indices of isolated and contracting heart metabolism. As a result it has been revealed that the weight of rats with II-type PD and abdominal adisposity, the level of glucose and glycated haemoglobin in blood, of lactate and pyruvate had been increased surely. The normal level of blood serum C-peptide has confirmed the absence of mass death of β-cells. The hearts taken from diabetic animals have responded to the increase of contraction frequency with the decrease of advanced pressure, i.e. the negative inotropic effect has been observed. Therefore the peripheral insulin resistance plays the leading role in the development of metabolic and functional abnormality complex at II-type PD and abdominal adisposity. Accumulation of lactate, metabolic acidosis, decrease of glucose efficiency and dysfunction of cardiac hystiocyte calcium pump with the development of diastolic myocardium dysfunction contribute to the development of metabolic disturbances.

EFFECT OF INSULIN ON HEART METABOLISM AND ACIDOSIS IN ISCHAEMIA: A 31P NMR STUDY

1981 ◽  
Vol 9 (2) ◽  
pp. 218P-218P
Author(s):  
Ian A. Bailey ◽  
A. -M. Seymour ◽  
S. R. Williams ◽  
G. K. Radda
Keyword(s):  
31P Nmr ◽  
Heart Metabolism ◽  
Nmr Study

Computer simulation of rat heart metabolism after adding glucose to the perfusate

1977 ◽  
Vol 232 (5) ◽  
pp. R175-R184 ◽  
Author(s):  
M. J. Achs ◽  
D. Garfinkel
Keyword(s):  
Krebs Cycle ◽  
Acid Oxidation ◽  
Allosteric Enzyme ◽  
Heart Metabolism ◽  
Rat Hearts ◽  
Cardiac Energy Metabolism ◽  
Perfused Rat Hearts ◽  
Alpha Ketoglutarate Dehydrogenase

An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system.

scholarly journals Hyperacetylation of Cardiac Mitochondrial Proteins Is Associated with Metabolic Impairment and Sirtuin Downregulation after Chronic Total Body Irradiation of ApoE -/- Mice

2019 ◽  
Vol 20 (20) ◽  
pp. 5239 ◽  
Author(s):  
Zarko Barjaktarovic ◽  
Juliane Merl-Pham ◽  
Ignacia Braga-Tanaka ◽  
Satoshi Tanaka ◽  
Stefanie M. Hauck ◽  
...  
Keyword(s):  
Low Dose ◽  
Great Majority ◽  
Tca Cycle ◽  
Heart Mitochondria ◽  
Acid Oxidation ◽  
Cardiac Damage ◽  
Heart Metabolism ◽  
Increased Risk ◽  
Radiation Induced ◽  
Total Body

Chronic exposure to low-dose ionizing radiation is associated with an increased risk of cardiovascular disease. Alteration in energy metabolism has been suggested to contribute to radiation-induced heart pathology, mitochondrial dysfunction being a hallmark of this disease. The goal of this study was to investigate the regulatory role of acetylation in heart mitochondria in the long-term response to chronic radiation. ApoE-deficient C57Bl/6J mice were exposed to low-dose-rate (20 mGy/day) gamma radiation for 300 days, resulting in a cumulative total body dose of 6.0 Gy. Heart mitochondria were isolated and analyzed using quantitative proteomics. Radiation-induced proteome and acetylome alterations were further validated using immunoblotting, enzyme activity assays, and ELISA. In total, 71 proteins showed peptides with a changed acetylation status following irradiation. The great majority (94%) of the hyperacetylated proteins were involved in the TCA cycle, fatty acid oxidation, oxidative stress response and sirtuin pathway. The elevated acetylation patterns coincided with reduced activity of mitochondrial sirtuins, increased the level of Acetyl-CoA, and were accompanied by inactivation of major cardiac metabolic regulators PGC-1 alpha and PPAR alpha. These observations suggest that the changes in mitochondrial acetylation after irradiation is associated with impairment of heart metabolism. We propose a novel mechanism involved in the development of late cardiac damage following chronic irradiation.

Oscillations of Intramuscular pH in Perfused Rat Heart

1973 ◽  
Vol 51 (3) ◽  
pp. 234-238 ◽  
Author(s):  
Naranjan S. Dhalla ◽  
John C. Yates ◽  
Israel Kleinberg
Keyword(s):  
Cardiac Muscle ◽  
Rat Heart ◽  
Cardiac Contraction ◽  
Mechanical Activity ◽  
Heart Metabolism ◽  
Relaxation Cycle ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Metabolic Stimulation ◽  
Intramuscular Ph

The intramuscular pH of the isolated perfused rat heart fluctuated between 7.11 and 7.14 during each contraction–relaxation cycle; the pH began to decline prior to the onset of cardiac contraction. The observed pH oscillations are independent of the mechanical activity and seem to reflect cyclic fluctuations in heart metabolism during the process of "excitation – metabolic stimulation" in the cardiac muscle.

EFFECT OF MODERATE INTENSITY ENDURANCE TRAINING ON RAT HEART METABOLISM

1998 ◽  
Vol 30 (Supplement) ◽  
pp. 16
Author(s):  
M. L. Zonderland ◽  
P. R. B??r ◽  
J. C. Reijneveld ◽  
B. M. Spruijt ◽  
H. A. Keizer ◽  
...  
Keyword(s):  
Endurance Training ◽  
Rat Heart ◽  
Moderate Intensity ◽  
Heart Metabolism

scholarly journals Infusion of a biotinylated bis-glucose photolabel: a new method to quantify cell surface GLUT4 in the intact mouse heart

2007 ◽  
Vol 292 (6) ◽  
pp. E1922-E1928 ◽  
Author(s):  
Edward J. Miller ◽  
Ji Li ◽  
Kevin M. Sinusas ◽  
Geoffrey D. Holman ◽  
Lawrence H. Young
Keyword(s):  
Cell Surface ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Metabolic Stress ◽  
Glucose Transporters ◽  
Mouse Heart ◽  
Perfused Heart ◽  
Heart Metabolism ◽  
Intact Mouse ◽  
Novel Approach

Glucose uptake in the heart is mediated by specific glucose transporters (GLUTs) present on cardiomyocyte cell surface membranes. Metabolic stress and insulin both increase glucose transport by stimulating the translocation of glucose transporters from intracellular storage vesicles to the cell surface. Isolated perfused transgenic mouse hearts are commonly used to investigate the molecular regulation of heart metabolism; however, current methods to quantify cell surface glucose transporter content in intact mouse hearts are limited. Therefore, we developed a novel technique to directly assess the cell surface content of the cardiomyocyte glucose transporter GLUT4 in perfused mouse hearts, using a cell surface impermeant biotinylated bis-glucose photolabeling reagent (bio-LC-ATB-BGPA). Bio-LC-ATB-BGPA was infused through the aorta and cross-linked to cell surface GLUTs. Bio-LC-ATB-BGPA-labeled GLUT4 was recovered from cardiac membranes by streptavidin isolation and quantified by immunoblotting. Bio-LC-ATB-BGPA-labeling of GLUT4 was saturable and competitively inhibited by d-glucose. Stimulation of glucose uptake by insulin in the perfused heart was associated with parallel increases in bio-LC-ATB-BGPA-labeling of cell surface GLUT4. Bio-LC-ATB-BGPA also labeled cell surface GLUT1 in the perfused heart. Thus, photolabeling provides a novel approach to assess cell surface glucose transporter content in the isolated perfused mouse heart and may prove useful to investigate the mechanisms through which insulin, ischemia, and other stimuli regulate glucose metabolism in the heart and other perfused organs.

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