PICOT Inhibits Cardiac Hypertrophy and Enhances Ventricular Function and Cardiomyocyte Contractility

Jeong, Dongtak; Cha, Hyeseon; Kim, Eun Young; Kang, Misuk; Yang, Dong Kwon; Kim, Ji Myoung; Yoon, Pyoung Oh; Oh, Jae Gyun; Bernecker, Oliver Y.; Satoh, Susumu; Thư, Le Thi Anh; Cui, Lei; Lee, Younghoon; Kim, Do Han; Woo, Sun–Hee; Liao, Ronglih; Hajjar, Roger J.; Park, Woo Jin

doi:10.1161/01.res.0000234780.06115.2c

Cited by 78 publications

(69 citation statements)

References 40 publications

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“…Ventricular myocytes were isolated from Sprague-Dawley male rats (body weight 280-300 g) via enzymatic dissociation as described previously [18]. Briefly, the heart was retrogradely perfused for 5 minutes with a Tyrode buffer (137 mM NaCl, 5.4 mM KCl, 1 mM CaCl 2 , 1 mM MgCl 2 , 10 mM Glucose, 0.5 mM taurine and 10 mM HEPES (pH 7.4)) then switched to an enzyme solution containing collagenase II (Worthington) and hyaluronidase II (Sigma) for additional 10 to 15 minutes.…”

Section: Preparation Of Adult Cardiomyocytesmentioning

confidence: 99%

Role of resistin in cardiac contractility and hypertrophy

Kim

Satoh

et al. 2008

Journal of Molecular and Cellular Cardiology

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Cardiovascular sequelae including diabetic cardiomyopathy constitute the major cause of death in diabetic patients. Although several factors may contribute to the development of this cardiomyopathy, the underlying molecular/cellular mechanisms leading to cardiac dysfunction are still partially understood. Recently, a novel paradigm for the role of the adipocytokine resistin in diabetes has emerged. Resistin has been proposed to be a link between obesity, insulin resistance and diabetes. Using microarray analysis, we have recently found that cardiomyocytes isolated from type 2 diabetic hearts express high levels of resistin. However, the function of resistin with respect to cardiac function is unknown. In this study we show that resistin is not only expressed in the heart, but also promotes cardiac hypertrophy. Adenovirus-mediated overexpression of resistin in cultured neonatal rat ventricular myocytes (NRVM) significantly increased sarcomere organization and cell size, increased protein synthesis and increased the expression of atrial natriuretic factor and β-myosin heavy chain. Overexpression of resistin in NRVM was also associated with activation of the mitogenactivated protein (MAP) kinases, ERK1/2 and p38, as well as increased Ser-636 phosphorylation of insulin receptor substrate-1 (IRS-1), indicating that IRS-1/MAPK pathway may be involved in the observed hypertrophic response. Overexpression of resistin in adult cultured cardiomyocytes significantly altered myocyte mechanics by depressing cell contractility as well as contraction and relaxation velocities. Intracellular Ca 2+ measurements showed slower Ca 2+ transients decay in resistin-transduced myocytes compared to controls, suggesting impaired cytoplasmic Ca 2+ clearing or alterations in myofilament activation. We conclude that resistin overexpression alters cardiac contractility, confers to primary cardiomyocytes all the features of the hypertrophic phenotype and promotes cardiac hypertrophy possibly via the IRS-1/MAPK pathway.

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Section: Preparation Of Adult Cardiomyocytesmentioning

confidence: 99%

Role of resistin in cardiac contractility and hypertrophy

Kim

Satoh

et al. 2008

Journal of Molecular and Cellular Cardiology

Self Cite

141

120

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“…After 2 weeks of baseline echocardiographic monitoring, TAB or sham surgery was performed as previously described (Jeong et al, 2006). Specifically, the mice were anesthetized with 1 × Avertin by intraperitoneal injection and their breathing was controlled with a ventilator (Harvard Apparatus) while the mice were on heating pad, with a tidal volume of 0.1 ml and a respiratory rate of 120 breaths per minute.…”

Section: Transverse Aortic Banding (Tab)mentioning

confidence: 99%

“…Frozen hearts were grinded to powder with liquid nitrogen. Half of the powder was used to prepare total RNA using the TRI reagent (Sigma) as previously described (Jeong et al, 2006). Reverse-transcription was performed using ImProm II reverse-transcriptase (Promega) with oligo-dT priming.…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

Parathyroid hormone accelerates decompensation following left ventricular hypertrophy

et al. 2010

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Abbreviations: FS, fractional shortening; LVH, left ventricular hypertrophy; LVIDs, left ventricular internal dimension at systole; LVPWs, left ventricular posterior wall thickness at systole; PTH, parathyroid hormone; TAB, transverse aortic banding AbstractParathyroid hormone (PTH) treatment was previously shown to improve cardiac function after myocardial infarction by enhancing neovascularization and cell survival. In this study, pressure overload-induced left ventricular hypertrophy (LVH) was induced in mice by transverse aortic banding (TAB) for 2 weeks. We subsequently evaluated the effects of a 2-week treatment with PTH or saline on compensated LVH. After another 4 weeks, the hearts of the mice were analyzed by echocardiography, histology, and molecular biology. Echocardiography showed that hearts of the PTH-treated mice have more severe failing phenotypes than the saline-treated mice following TAB with a greater reduction in fractional shortening and left ventricular posterior wall thickness and with a greater increase in left ventricular internal dimension. Increases in the heart weight to body weight ratio and lung weight to body weight ratio following TAB were significantly exacerbated in PTH-treated mice compared to saline-treated mice. Molecular markers for heart failure, fibrosis, and angiogenesis were also altered in accordance with more severe heart failure in the PTH-treated mice compared to the saline-treated mice following TAB. In addition, the PTH-treated hearts were manifested with increased fibrosis accompanied by an enhanced SMAD2 phosphorylation. These data suggest that the PTH treatment may accelerate the process of decompensation of LV, leading to heart failure.

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“…The protein interacting cousin of thioredoxin, PICOT, acts as an inducible inhibitor of hypertrophy. In addition, this protein has direct effects on contractile function (189,408). PICOT was discovered in a yeast-2 hybrid screen and showed 30% homology with thioredoxin (973).…”

Section: Other Targetsmentioning

confidence: 99%

Designing Heart Performance by Gene Transfer

Davis¹,

Westfall²,

Townsend³

et al. 2008

Physiological Reviews

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The birth of molecular cardiology can be traced to the development and implementation of high-fidelity genetic approaches for manipulating the heart. Recombinant viral vector-based technology offers a highly effective approach to genetically engineer cardiac muscle in vitro and in vivo. This review highlights discoveries made in cardiac muscle physiology through the use of targeted viral-mediated genetic modification. Here the history of cardiac gene transfer technology and the strengths and limitations of viral and nonviral vectors for gene delivery are reviewed. A comprehensive account is given of the application of gene transfer technology for studying key cardiac muscle targets including Ca2+handling, the sarcomere, the cytoskeleton, and signaling molecules and their posttranslational modifications. The primary objective of this review is to provide a thorough analysis of gene transfer studies for understanding cardiac physiology in health and disease. By comparing results obtained from gene transfer with those obtained from transgenesis and biophysical and biochemical methodologies, this review provides a global view of cardiac structure-function with an eye towards future areas of research. The data presented here serve as a basis for discovery of new therapeutic targets for remediation of acquired and inherited cardiac diseases.

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PICOT Inhibits Cardiac Hypertrophy and Enhances Ventricular Function and Cardiomyocyte Contractility

Cited by 78 publications

References 40 publications

Role of resistin in cardiac contractility and hypertrophy

Role of resistin in cardiac contractility and hypertrophy

Parathyroid hormone accelerates decompensation following left ventricular hypertrophy

Designing Heart Performance by Gene Transfer

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