Glycogen Synthase Kinase-3β Regulates Post–Myocardial Infarction Remodeling and Stress-Induced Cardiomyocyte Proliferation In Vivo

Woulfe, Kathleen C.; Gao, Erhe; Lal, Hind; Harris, David; Fan, Qian; Vagnozzi, Ronald J.; DeCaul, Morgan; Shang, Xianwen; Patel, Satish; Woodgett, James R.; Force, Thomas; Zhou, Jibin

doi:10.1161/circresaha.109.211482

Cited by 109 publications

(133 citation statements)

References 51 publications

(60 reference statements)

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“…In a pressure-overload model in rats, inhibition of GSK3β with LiCl is suggested to accelerate the development of cardiac hypertrophy through a β-catenin-dependent mechanism (233). Conditional GSK3β knock-out in mice did not have any effect on TAC-induced cardiac hypertrophy compared to control animals (262). On the contrary, transgenic mice carrying a dominant negative form of GSK3β-developed physiological hypertrophy (without experimental procedures) as demonstrated by increased left ventricular weight/body weight ratios and increased cardiac contractility, whereas the extent of TAC induced hypertrophy was not affected in these transgenic mice (91).…”

Section: Gsk3β and Cardiac Hypertrophymentioning

confidence: 80%

“…Favorable cardiac remodeling is thought to be promoted by increased proliferation of differentiated cardiomyocytes in the remote myocardium, as demonstrated by increased amount of proliferating cells. Inducible cardiomyocyte-specific knock-out of GSK3β following MI led to less ventricular dilatation and more preserved cardiac function at 8 weeks after MI, although there was no difference in ejection fraction at 1 week after MI (262). This could implicate that deletion of the GSK3β gene does not have a direct effect on the scar formation or wound healing, as also demonstrated by similar infarct size between groups, but apparently affects cardiomyocytes to become hypertrophic and reinforce cardiac function as was seen by increased cross-sectional areas of the knock-out cardiomyocytes.…”

Section: Modulation Of the β-Catenin Degradation Complexmentioning

confidence: 91%

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Wnt Signaling in Cardiac Disease

Hermans

Blankesteijn

2015

Comprehensive Physiology

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Wnt signaling encompasses multiple and complex signaling cascades and is involved in many developmental processes such as tissue patterning, cell fate specification, and control of cell division. Consequently, accurate regulation of signaling activities is essential for proper embryonic development. Wnt signaling is mostly silent in the healthy adult organs but a reactivation of Wnt signaling is generally observed under pathological conditions. This has generated increasing interest in this pathway from a therapeutic point of view. In this review article, the involvement of Wnt signaling in cardiovascular development will be outlined, followed by its implication in myocardial infarct healing, cardiac hypertrophy, heart failure, arrhythmias, and atherosclerosis. The initial experiments not always offer consensus on the effects of activation or inactivation of the pathway, which may be attributed to (i) the type of cardiac disease, (ii) timing of the intervention, and (iii) type of cells that are targeted. Therefore, more research is needed to determine the exact implication of Wnt signaling in the conditions mentioned above to exploit it as a powerful therapeutic target.

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Section: Gsk3β and Cardiac Hypertrophymentioning

confidence: 80%

Section: Modulation Of the β-Catenin Degradation Complexmentioning

confidence: 91%

Wnt Signaling in Cardiac Disease

Hermans

Blankesteijn

2015

Comprehensive Physiology

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“…Consistent with this concept, homozygous GSK-3α knockout mice develop cardiac hypertrophy and contractile dysfunction two months after birth [9]. Homozygous GSK-3β knockout mice are embryonic lethal [7,10,11] and adult cardiomyocytespecific conditional GSK-3β knockout mice show increased cardiomyocyte proliferation [12]. Furthermore, deletion of GSK-3β in embryonic stem cells increases cardiomyocyte proliferation and inhibits differentiation of embryonic stem cells into cardiomyocytes [11,13].…”

mentioning

confidence: 82%

GSK-3 Inhibitors: Anti-Diabetic Treatment Associated with Cardiac Risk?

Nabben

Neumann

2016

Cardiovasc Drugs Ther

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“…Conditional deletion of GSK-3b, specifically in cardiomyocytes, has been shown to have no effect on cardiac fibrosis after MI. 46 Besides, lithium, a nonselective GSK-3 inhibitor, inhibits both isoforms of GSK-3. Upregulation of GSK-3a in cardiac-specific GSK-3a transgenic mice increases cardiac fibrosis pressure overload-induced cardiac hypertrophy.…”

Section: Previous Studiesmentioning

confidence: 99%

Inhibition of glycogen synthase kinase-3β prevents sympathetic hyperinnervation in infarcted rats

Lee

Lin

Chang

2015

Exp Biol Med (Maywood)

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We have demonstrated that nerve growth factor (NGF) expression in the myocardium is selectively increased during chronic stage of myocardial infarction, resulting in sympathetic hyperinnervation. Glycogen synthase kinase-3 (GSK-3) signal has been shown to play key roles in the regulation of cytoskeletal assembly during axon regeneration. We assessed whether lithium, a GSK-3 inhibitor, attenuates cardiac sympathetic reinnervation after myocardial infarction through attenuated NGF expression and Tau expression. Twenty-four hours after ligation of the anterior descending artery, male Wistar rats were randomized to either LiCl or SB216763, chemically unrelated inhibitors of GSK-3b, a combination of LiCl and SB216763, or vehicle for four weeks. Myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats compared with sham-operated rats, consistent with excessive sympathetic reinnervation after infarction. Immunohistochemical analysis for sympathetic nerve also confirmed the change of myocardial norepinephrine. This was paralleled by a significant upregulation of NGF protein and mRNA in the vehicletreated rats, which was reduced after administering either LiCl, SB216763, or combination. Arrhythmic scores during programmed stimulation in the vehicle-treated rats were significantly higher than those treated with GSK-3 inhibitors. Addition of SB216763 did not have additional beneficial effects compared with those seen in rats treated with LiCl alone. Furthermore, lithium treatment increased Tau1 and decreased AT8 and AT180 levels. Chronic use of lithium after infarction, resulting in attenuated sympathetic reinnervation by GSK-3 inhibition, may modify the arrhythmogenic response to programmed electrical stimulation.Keywords: Arrhythmias, glycogen synthase kinase-3, lithium, myocardial infarction, Tau protein Experimental Biology and Medicine 2015; 240: 979-992.

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Glycogen Synthase Kinase-3β Regulates Post–Myocardial Infarction Remodeling and Stress-Induced Cardiomyocyte Proliferation In Vivo

Cited by 109 publications

References 51 publications

Wnt Signaling in Cardiac Disease

Wnt Signaling in Cardiac Disease

GSK-3 Inhibitors: Anti-Diabetic Treatment Associated with Cardiac Risk?

Inhibition of glycogen synthase kinase-3β prevents sympathetic hyperinnervation in infarcted rats

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