Cardiac Hypertrophy by Hypertension and Exercise Training Exhibits Different Gene Expression of Enzymes in Energy Metabolism

Iemitsu, Motoyuki; Miyauchi, Takashi; Maeda, Seiji; Sakai, Satoshi; Fujii, Nobuharu; Miyazaki, Hitoshi; Kakinuma, Yoshihiko; Matsuda, Mitsuo; Yamaguchi, Iwao

doi:10.1291/hypres.26.829

Cited by 65 publications

(50 citation statements)

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“…6 and Ref. 21, respectively) suggest the presence of other, yet-to-be identified, regulatory mechanism(s), which could compensate CD36 deficiency. One potential mechanism is activation of AMP-dependent protein kinase due to high circulating levels of leptin or angiotensin II in SHR (7,33,41,53).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, O'Donnell et al (35) presented evidence for a limitation in the transfer of cytosolic NADH to mitochondria when glycolytic flux is enhanced in normal hearts subjected to high workload. This limitation could become even more important in SHR hearts, which have an intrinsically elevated glycolytic activity associated with increased mRNA levels for phosphofructokinase and LDH (8,21,57 (25), and a reduced calcium transport in the sarcoplasmic reticulum (29), possibly through an inhibitory effect of cytosolic NADH on cardiac ryanodine receptors (61). Furthermore, it may favor free radical production by 1) activating cardiomyocyte NAD(P)H oxidase (31), an enzyme that is more highly expressed in SHR hearts (41); or 2) inducing the formation of the unstable ubisemiquinone radical (49).…”

Section: Discussionmentioning

confidence: 99%

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Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid

Labarthe

Khairallah²,

Bouchard³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Des Rosiers. Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid. Am J Physiol Heart Circ Physiol 288: H1425-H1436, 2005. First published November 18, 2004; doi:10.1152/ajpheart.00722.2004.-The spontaneously hypertensive rat (SHR) is a model of cardiomyopathy characterized by a restricted use of exogenous long-chain fatty acid (LCFA) for energy production. The aims of the present study were to document the functional and metabolic response of the SHR heart under conditions of increased energy demand and the effects of a medium-chain fatty acid (MCFA; octanoate) supplementation in this situation. Hearts were perfused ex vivo in a working mode with physiological concentrations of substrates and hormones and subjected to an adrenergic stimulation (epinephrine, 10 M).13 C-labeled substrates were used to assess substrate selection for energy production. Compared with control Wistar rat hearts, SHR hearts showed an impaired response to the adrenergic stimulation as reflected by 1) a smaller increase in contractility and developed pressure, 2) a faster decline in the aortic flow, and 3) greater cardiac tissue damage (lactate dehydrogenase release: 1,577 Ϯ 118 vs. 825 Ϯ 44 mU/min, P Ͻ 0.01). At the metabolic level, SHR hearts presented 1) a reduced exogenous LCFA contribution to the citric acid cycle flux (16 Ϯ 1 vs. 44 Ϯ 4%, P Ͻ 0.001) and an enhanced contribution of endogenous substrates (20 Ϯ 4 vs. 1 Ϯ 4%, P Ͻ 0.01); and 2) an increased lactate production from glycolysis, with a greater lactate-to-pyruvate production ratio. Addition of 0.2 mM octanoate reduced lactate dehydrogenase release (1,145 Ϯ 155 vs. 1,890 Ϯ 89 mU/min, P Ͻ 0.001) and increased exogenous fatty acid contribution to energy metabolism (23.7 Ϯ 1.3 vs. 15.8 Ϯ 0.8%, P Ͻ 0.01), which was accompanied by an equivalent decrease in unlabeled endogenous substrate contribution, possibly triglycerides (11.6 Ϯ 1.5 vs. 19.0 Ϯ 1.2%, P Ͻ 0.01). Taken altogether, these results demonstrate that the SHR heart shows an impaired capacity to withstand an acute adrenergic stress, which can be improved by increasing the contribution of exogenous fatty acid oxidation to energy production by MCFA supplementation. isolated working rat heart perfusion; citric acid cycle;13 C mass isotopomer analysis; fatty acid translocase/CD36; epinephrine ACCUMULATING EVIDENCE INDICATES that alterations in substrate selection for energy production can affect the heart's susceptibility to injury as well as the development of hypertrophy and heart failure (2,8,19,47,57). Specifically, interventions favoring carbohydrate over fatty acid (FA) oxidation were repeatedly shown to enhance the function of the ischemicreperfused heart (27, 51) or the failing heart (51). This notion has led to the development of new drugs, such as ranolazine, oxfenicine, and trimetazidine, whose effects are attributed to inhibition of FA oxidation (47, 51). What remains to be clarified, however, is how much can FA oxid...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid

Labarthe

Khairallah²,

Bouchard³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…It has been described that the energy production in cardiac hypertrophy in SHR showed a shift from the use of fatty acids toward the use of glucose (27). Iemitsu et al showed that the mRNA expression of key enzymes in the glycolytic metabolic pathway was markedly increased in the SHR hearts, indicating a decline of cardiac function (28). Diastolic dysfunction is to be expected in the SHR because of the increased wall thickness and fibrosis (29−31).…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Evaluation of the Time Course of Change in Cardiac Function in Spontaneously Hypertensive Rats by Echocardiography

et al. 2005

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“…On the protein level, in cardiac muscle cells ATP and citrate concentrations are so high that the enzyme would be completely inhibited and therefore could not act as an allosteric regulated key enzyme (38). Interestingly, PFK mRNA was markedly higher in spontaneously hypertensive rats compared with control rats and remained unchanged by exercise training-induced cardiac hypertrophy compared with controls (19).…”

Section: Cardiac Gene Expression In Dtgrmentioning

confidence: 99%

Cardiac gene expression profile in rats with terminal heart failure and cachexia

Wellner

Dechend

Park

et al. 2005

Physiological Genomics

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About one-half of double transgenic rats (dTGR) overexpressing the human renin and angiotensinogen genes die by age 7 wk of terminal heart failure (THF); the other (preterminal) one-half develop cardiac damage but survive. Our study’s aim was to elucidate cardiac gene expression differences in dTGR-THF compared with dTGR showing compensated cardiac hypertrophy but not yet THF. dTGR treated with losartan (LOS) and nontransgenic rats (SD) served as controls. THF-dTGR body weight was significantly lower than for all other groups. At death, THF-dTGR had blood pressures of 228 ± 7 mmHg (cardiac hypertrophy index 6.2 ± 0.1 mg/g). Tissue Doppler showed reduced peak early (Ea) to late (Aa) diastolic expansion in THF-dTGR, indicating diastolic function. Preterminal dTGR had blood pressures of 197 ± 5 mmHg (cardiac hypertrophy index 5.1 ± 0.1 mg/g); Ea < Aa compared with LOS-dTGR (141 ± 6 mmHg; 3.7±0.1 mg/g; Ea > Aa) and SD (112 ± 4 mmHg; 3.6 ± 0.1 mg/g; Ea > Aa). Left ventricular RNA was isolated for the Affymetrix system and TaqMan RT-PCR. THF-dTGR and dTGR showed upregulation of hypertrophy markers and α/β-myosin heavy chain switch to the fetal isoform. THF-dTGR (vs. dTGR) showed upregulation of 239 and downregulation of 150 genes. Various genes of mitochodrial respiratory chain and lipid catabolism were reduced. In addition, genes encoding transcription factors (CEBP-β, c-fos, Fra-1), coagulation, remodeling/repair components (HSP70, HSP27, heme oxygenase), immune system (complement components, IL-6), and metabolic pathway were differentially expressed. In contrast, LOS-dTGR and SD had similar expression profiles. These data demonstrate that THF-dTGR show an altered expression profile compared with preterminal dTGR.

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Cardiac Hypertrophy by Hypertension and Exercise Training Exhibits Different Gene Expression of Enzymes in Energy Metabolism

Cited by 65 publications

References 48 publications

Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid

Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid

Noninvasive Evaluation of the Time Course of Change in Cardiac Function in Spontaneously Hypertensive Rats by Echocardiography

Cardiac gene expression profile in rats with terminal heart failure and cachexia

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