Thyroid hormone improves function and Ca2+ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca2+-ATPase and alpha-myosin heavy chain in rat hearts.

Chang, Kevin; Figueredo, Vincent M.; Schreur, J. H. M.; Kariya, Ken-ichi; Weiner, Michael W.; Simpson, Paul C.; Camacho, S. Albert

doi:10.1172/jci119699

Cited by 88 publications

(56 citation statements)

References 52 publications

(65 reference statements)

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“…This has also been observed in a variety of cardiomyopathies, including that induced by prolonged (Ͼ 12 wk) aortic banding (45). Although the decrease in cytosolic calcium after stimulation depends on several processes, the most quantitatively important are through reuptake of calcium into the sarcoplasmic reticulum and extrusion out of the cell via the sodium calcium exchanger.…”

Section: Discussionmentioning

confidence: 76%

Effect of Chronic Renal Failure on Cardiac Contractile Function, Calcium Cycling, and Gene Expression of Proteins Important for Calcium Homeostasis in the Rat

Kennedy

Omran

Periyasamy

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Patients with chronic renal failure frequently develop cardiac hypertrophy and diastolic dysfunction; however, the mechanisms by which this occurs are still unclear. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy and studied for their isolated myocyte function, calcium cycling, and gene expression of proteins important in calcium homeostasis after 4 wk. Comparable rats subjected to suprarenal aortic banding for the same duration were used for comparison. Rats subjected to 5/6 nephrectomy and aortic banding developed comparable hypertension; however, rats subjected to 5/6 nephrectomy experienced a greater degree of cardiac hypertrophy and downregulation of cardiac sodium potassium ATPase (Na ϩ /K ϩ -ATPase) activity than rats subjected to aortic banding. Moreover, cells isolated from the 5/6 nephrectomy rat hearts displayed impaired contractile function and altered calcium cycling compared with cells isolated from control or aortic constriction rat hearts. The 5/6 nephrectomy rat heart cells displayed a prolonged time constant for calcium recovery following stimulation, which corresponded to decreases in homogenate sarcoplasmic reticulum calcium ATPase-2a (SERCA2a) activity, protein density, and mRNA for SERCA2a. In conclusion, chronic renal failure leads to alterations in cardiac gene expression, which produces alterations in cardiac calcium cycling and contractile function. These changes cannot be explained only by the observed increases in BP. jshapiro@mco.eduPatients with renal failure usually develop cardiac complications. In end-stage renal disease (ESRD) patients treated with hemodialysis in the United States, annual mortality rates exceed 20%, with more than 50% attributed to cardiac mortality (1). Although the term "uremic cardiomyopathy" had previously been used to refer to a dilated cardiomyopathy complicating renal failure, more recent studies suggest that the most common form of heart disease in renal failure patients is one characterized by diastolic dysfunction and left ventricular hypertrophy (2). Although a number of known factors have been implicated in the pathogenesis of the left ventricular hypertrophy and diastolic dysfunction, our understanding of these processes is still incomplete (3).For many years, it has been known that the sodium pump is abnormal in chronic renal failure and that circulating inhibitor(s) can be demonstrated in the serum of uremic patients (4 -6). We have observed that sodium pump inhibition initiates a signal cascade that can cause alterations in gene transcription and ultimately produce hypertrophy in cardiomyocytes grown in culture (7-9). We have also observed that sodium pump inhibitors, including those circulating in the serum of uremic patients, can acutely cause altered calcium cycling and cardiomyocyte relaxation through sodium pump inhibition (10). The following studies were performed to further examine how cardiac growth and function are chronically modified by the uremic milieu. Materials and Methods AnimalsMale Sprague-Dawley rats (200...

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Section: Discussionmentioning

confidence: 76%

Effect of Chronic Renal Failure on Cardiac Contractile Function, Calcium Cycling, and Gene Expression of Proteins Important for Calcium Homeostasis in the Rat

Kennedy

Omran

Periyasamy

et al. 2003

Journal of the American Society of Nephrology

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“…Increases in ␣MHC are frequently observed in physiological hypertrophy. 26 Fourth, neither fibrosis nor apoptosis was increased in conjunction with cardiac hypertrophy in Tg-GSK-3␤-DN. Fifth, GSK-3␤-DN and swimming exercise failed to show completely additive effects on cardiac hypertrophy, suggesting that GSK-3␤-DN and exercise induce hypertrophy partially through a common mechanism.…”

Section: Discussionmentioning

confidence: 91%

Inhibition of Glycogen Synthase Kinase 3β During Heart Failure Is Protective

Hirotani

Zhai

Tomita

et al. 2007

Circulation Research

106

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Abstract-Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3␤ in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3␤ (Tg-GSK-3␤-DN) and tetracycline-regulatable wild-type GSK-3␤. GSK-3␤-DN significantly reduced the kinase activity of endogenous GSK-3␤, inhibited phosphorylation of eukaryotic translation initiation factor 2B, and induced accumulation of ␤-catenin and myeloid cell leukemia-1, confirming that GSK-3␤-DN acts as a dominant negative in vivo. Tg-GSK-3␤-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the ␣-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater E max after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3␤ induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3␤-DN and nontransgenic mice, Tg-GSK-3␤-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3␤ transgene in tetracycline-regulatable wild-type GSK-3␤ mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3␤-DN in cardiac myocytes inhibited tumor necrosis factor-␣-induced apoptosis, and the antiapoptotic effect of GSK-3␤-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3␤ induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3␤ inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3␤ during heart failure could be compensatory. Key Words: GSK-3␤ Ⅲ heart failure Ⅲ cardiac hypertrophy Ⅲ apoptosis G SK-3␤ is a ubiquitously expressed serine/threonine kinase that has versatile biological functions in cells, including regulation of metabolism, cell growth/death, and protein translation and transcription. 1,2 Unlike most protein kinases, GSK-3␤ remains active in the resting state and is inactivated when cells are stimulated by mitogens, by other protein kinases, such as Akt, or by the Wnt pathway. In cardiac myocytes, GSK-3␤ phosphorylates ␤-catenin, 3 eukaryotic translation initiation factor (eIF)2B, 4 NFAT, 5 GATA4, 6 myocardin, 7 and other proteins, thereby negatively regulating protein synthesis and gene expression. GSK-3␤ downregulates SERCA2a 8 and enhances mitochondrial permeability transition, 9 thereby leading to an inability to normalize cytosolic Ca 2ϩ in diastole and reduced cell survival, respectively.GSK-3␤ is an important negative regulator of cardiac hypertrophy. 10 GSK-3␤ negatively regulates ␤-adrenergic and endothelin-induced cardiac hypertrophy in cultured ...

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“…In human failing hearts the αMHC isoform, which is nearly 10% of the total MHC pool, decreased to nearly non-detectable levels, and this was suggested to be a critical determinant of transition of the heart from adaptive hypertrophy to failure [7,9]. This idea is supported by experiments in which blocking of the MHC isoform shift by thyroid-hormone intervention prevented the functional decompensation of the heart in an aortic-banding model of heart failure [108]. However, because of the relatively low levels of αMHC in human hearts (~10% protein), others have disputed the concept of the shift in MHC isoforms as a major cause of muscle dysfunction of human failing hearts [109].…”

Section: Cardiac Hypertrophymentioning

confidence: 95%

“…A direct association of serum thyroid hormone levels with an α-to βMHC switch during cardiac hypertrophy has not been found; however, defects in the expression levels of thyroid receptors (TRα1, TRβ1 and TRα2) have been documented [58]. Treatment of animals with T4 or thyromimetic agent, DITPA, (diiodothyropropionic acid) reversed the myosin isoform switch as well as contractile dysfunctions associated with hypertrophy and heart failure, suggesting that a defect in thyroidhormone signaling may, in part, contribute to the MHC isoform distribution accompanied with the failing heart [108,117]. By promoter analysis of the αMHC gene, a number of negative regulatory DNA elements and their cognate binding factors have been identified.…”

Section: Cardiac Hypertrophymentioning

confidence: 99%

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

Gupta

2007

Journal of Molecular and Cellular Cardiology

190

171

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Thyroid hormone improves function and Ca2+ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca2+-ATPase and alpha-myosin heavy chain in rat hearts.

Cited by 88 publications

References 52 publications

Effect of Chronic Renal Failure on Cardiac Contractile Function, Calcium Cycling, and Gene Expression of Proteins Important for Calcium Homeostasis in the Rat

Effect of Chronic Renal Failure on Cardiac Contractile Function, Calcium Cycling, and Gene Expression of Proteins Important for Calcium Homeostasis in the Rat

Inhibition of Glycogen Synthase Kinase 3β During Heart Failure Is Protective

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

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