Accelerated Cardiomyopathy in Mice With Overexpression of Cardiac G
            <sub>s</sub>
            α and a Missense Mutation in the α-Myosin Heavy Chain

Hardt, Stefan E.; Geng, Yong–Jian; Montagne, Olivier; Asai, Kuniya; Hong, Chull; Yang, Gui Ping; Bishop, Sanford P.; Kim, Song Jung; Vatner, Dorothy E.; Seidman, Christine E.; Homcy, Charles J.; Vatner, Stephen F.

doi:10.1161/hc0502.103012

Cited by 27 publications

(26 citation statements)

References 20 publications

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“…114 Moreover, in some circumstances, overstimulation of the adrenergic signaling can cause or exacerbate the heart failure. 114,118,119 Despite these caveats, our interpretation of the composite body of animal "rescue" studies is that increasing or maintaining contractility at critical times before or just after injurious cardiac stimuli can delay or eliminate heart failure. The applicability of these approaches to humans is an important unanswered question because inotropic interventions have rarely, if ever, been examined in the setting of presymptomatic cardiac dysfunction.…”

Section: Is Contractility a Good Target For Heartmentioning

confidence: 99%

“…119,124 We hypothesize that these treatments cause negative side effects, such as apoptosis, which further depress cardiac function and exacerbate heart failure, or cause arrhythmias that induce sudden death. This hypothesis predicts that approaches that increase inotropy without increasing cAMP or without persistently increasing Ca 2ϩ may produce beneficial effects associated with increased contractility without the detrimental effects associated with overstimulated adrenergic 118,119 and nonadrenergic 89 signaling cascades. Indeed, improving contractility should decrease activation of adrenergic signaling cascades by improving hemodynamics and thereby reducing sympathetic activation.…”

Section: Does It Matter How Contractility Is Preservedmentioning

confidence: 99%

“…Those that overstimulated adrenergic signaling worsened heart failure. 118,119 Selectively increasing Ca 2ϩ transients without activating cAMP improved function 88,93,108 but did not always reduce hypertrophy. 125 Normalizing adrenergic signaling with ␤ARK-ct can restore contractility, reduce hypertrophy, and reduce the risk of heart failure.…”

Section: Does It Matter How Contractility Is Preservedmentioning

confidence: 99%

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Is Depressed Myocyte Contractility Centrally Involved in Heart Failure?

Houser

Margulies

2003

Circulation Research

187

155

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Abstract-This review examines the evidence for and against the hypothesis that abnormalities in cardiac contractility initiate the heart failure syndrome and drive its progression. There is substantial evidence that the contractility of failing human hearts is depressed and that abnormalities of basal Ca 2ϩ regulation and adrenergic regulation of Ca 2ϩ signaling are responsible. The cellular and molecular defects that cause depressed myocyte contractility are not well established but seem to culminate in abnormal sarcoplasmic reticulum uptake, storage, and release. There are also strong links between Ca 2ϩ regulation, Ca 2ϩ signaling pathways, hypertrophy, and heart failure that need to be more clearly delineated. There is not substantial direct evidence for a causative role for depressed contractility in the initiation and progression of human heart failure, and some studies show that heart failure can occur without depressed myocyte contractility. Stronger support for a causal role for depressed contractility in the initiation of heart failure comes from animal studies where maintaining or improving contractility can prevent heart failure. Recent clinical studies in humans also support the idea that beneficial heart failure treatments, such as ␤-adrenergic antagonists, involve improved contractility. Current or previously used heart failure treatments that increase contractility, primarily by increasing cAMP, have generally increased mortality. Novel heart failure therapies that increase or maintain contractility or adrenergic signaling by selectively modulating specific molecules have produced promising results in animal experiments. How to reliably implement these potentially beneficial inotropic therapies in humans without introducing negative side effects is the major unanswered question in this field.

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Section: Is Contractility a Good Target For Heartmentioning

confidence: 99%

Section: Does It Matter How Contractility Is Preservedmentioning

confidence: 99%

Section: Does It Matter How Contractility Is Preservedmentioning

confidence: 99%

See 1 more Smart Citation

Is Depressed Myocyte Contractility Centrally Involved in Heart Failure?

Houser

Margulies

2003

Circulation Research

187

155

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“…The role of GSK-3␤ in the heart is still controversial. On one hand, GSK-3␤ is known to be a negative regulator of hypertrophy mainly regulated via Akt signaling (19,21). On the other hand, overexpression of wild-type GSK-3␤ in mice induces cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Transthoracic echocardiography was performed in a modified setting as previously described in detail (19). Experiments were recorded using a dynamic focused 10-MHz probe with an ATL 5000 echocardiography machine.…”

Section: Methodsmentioning

confidence: 99%

Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy

Buss

Riffel

Malekar

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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) for 4 wk starting 1 day after the induction of MI or AB. Exercisetrained animals received deguelin for 4 wk during the training period. In vitro, we observed reduced phosphorylation of Akt and glycogen synthase kinase (GSK)-3␤ after an incubation with deguelin, whereas MAPK signaling was not significantly affected. In vivo, treatment with deguelin led to attenuated phosphorylation of Akt and GSK-3␤ 4 wk after MI. These animals showed significantly increased heart weights and impaired LV function with increased end-diastolic diameters (12.0 Ϯ 0.3 vs. 11.1 Ϯ 0.3 mm, P Ͻ 0.05), end-diastolic volumes (439 Ϯ 8 vs. 388 Ϯ 18 l, P Ͻ 0.05), and cardiomyocyte sizes (ϩ20%, P Ͻ 0.05) compared with MI animals receiving vehicle treatment. Furthermore, activation of Ca 2ϩ /calmodulin-dependent kinase II in deguelin-treated MI animals was increased compared with the vehicle-treated group. Four wk after AB, we observed an augmentation of pathological hypertrophy in the deguelin-treated group with a significant increase in heart weights and cardiomyocyte sizes (Ͼ20%, P Ͻ 0.05). In contrast, the development of physiological hypertrophy was inhibited by deguelin treatment in exercise-trained animals. In conclusion, chronic Akt blockade with deguelin aggravates adverse myocardial remodeling and antagonizes physiological hypertrophy. cardiac remodeling; exercise training ISCHEMIC HEART DISEASE is still one of the leading causes of mortality worldwide (34). Myocardial ischemia and myocardial infarction (MI) lead to contractile dysfunction and remodeling even after sufficient reperfusion due to early coronary artery intervention. A major cost problem for public health is the development of heart failure in these patients (13). One of the most important factors for improving the prognosis after

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Titanium dioxide nanoparticle-induced dysfunction of cardiac hemodynamics is involved in cardiac inflammation in mice

Hong

Zhao

et al. 2016

J. Biomed. Mater. Res.

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In the past two decades, titanium dioxide nanoparticles (TiO NPs) have been extensively used in medicine, food industry and other daily life, while their possible interactions with the their influence and human body on human health remain not well understood. Thus, the study was designed to examine whether long-term exposure to TiO NPs cause myocardial dysfunction which is involved in cardiac lesions and alter expression of genes and proteins involving inflammatory response in the mouse heart. The findings showed that intragastric feeding for nine consecutive months with TiO NPs resulted in titanium accumulation, infiltration of inflammatory cells and apoptosis of heart, reductions in net increases of body weight, cardiac indices of function (LV systolic pressure, maximal rate of pressure increase over time, maximal rate of pressure decrease over time and coronary flow), and increases in heart indices, cardiac indices of function (LV end-diastolic pressure and heart rate) in mice. TiO NPs also decreased ATP production in the hearts. Furthermore, TiO NPs increased expression of nuclear factor-κB, interleukin-lβ and tumour necrosis factor-α, and reduced expression of anti-inflammatory cytokines including suppressor of cytokine signaling (SOCS) 1 and SOCS3 in the cardiac tissue. These results suggest that TiO NPs may modulate the cardiac function and expression of inflammatory cytokines. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2917-2927, 2016.

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Accelerated Cardiomyopathy in Mice With Overexpression of Cardiac G _s α and a Missense Mutation in the α-Myosin Heavy Chain

Abstract: These results show that the cardiomyopathy developed by G(s)alpha x403 mice is synergistic rather than additive, most likely owing to the elevated baseline function combined with enhanced responsiveness to sympathetic stimulation.

Cited by 27 publications

References 20 publications

Is Depressed Myocyte Contractility Centrally Involved in Heart Failure?

Is Depressed Myocyte Contractility Centrally Involved in Heart Failure?

Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy

Titanium dioxide nanoparticle-induced dysfunction of cardiac hemodynamics is involved in cardiac inflammation in mice

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Accelerated Cardiomyopathy in Mice With Overexpression of Cardiac G s α and a Missense Mutation in the α-Myosin Heavy Chain

Abstract: These results show that the cardiomyopathy developed by G(s)alpha x403 mice is synergistic rather than additive, most likely owing to the elevated baseline function combined with enhanced responsiveness to sympathetic stimulation.

Cited by 27 publications

References 20 publications

Is Depressed Myocyte Contractility Centrally Involved in Heart Failure?

Is Depressed Myocyte Contractility Centrally Involved in Heart Failure?

Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy

Titanium dioxide nanoparticle-induced dysfunction of cardiac hemodynamics is involved in cardiac inflammation in mice

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Product

Resources

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Accelerated Cardiomyopathy in Mice With Overexpression of Cardiac G _s α and a Missense Mutation in the α-Myosin Heavy Chain