Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils

Belus, Alexandra; Piroddi, Nicoletta; Ferrantini, Cecilia; Tesi, Chiara; Cazorla, Olivier; Toniolo, Luana; Drost, Maurice; Mearini, Giulia; Carrier, Lucie; Rossi, Alessandra; Mugelli, Alessandro; Cerbai, Elisabetta; Velden, Jolanda van der; Poggesi, Corrado

doi:10.1161/circresaha.110.220699

Cited by 44 publications

(50 citation statements)

References 45 publications

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“…These results show that in atrial myocytes without relevant TTs, increased myofilament sensitivity results in significantly reduced Ca 2+ release in the center of the cell. Increases in Ca 2+ sensitivity have been reported for skinned fibers from an RAP model in dogs (13) and from AF patients (38), suggesting increased Ca 2+ content normal in RAP despite a reduced RyR2 cluster size, RyR2 Ca 2+ sensitivity has to increase. Computational estimates show that this increase in RyR2 Ca 2+ sensitivity due to the putative effects of increased RyR2 phosphorylation at the PKA site Ser2804 would be achieved by a 2-fold increase in RyR2 P O.…”

Section: Discussionmentioning

confidence: 83%

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

Greiser¹,

Kerfant²,

Williams³

et al. 2014

J. Clin. Invest.

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104

163

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Section: Discussionmentioning

confidence: 83%

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

Greiser¹,

Kerfant²,

Williams³

et al. 2014

J. Clin. Invest.

Self Cite

104

163

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“…Even small differences in the MHC isoform composition of isolated cardiomyocytes can affect power output, with an increase in the amount of MHC-β being associated with reduced power [33–35]. However, an increase in the amount of MHC-β is associated with increased economy of myocardial contraction [36], potentially providing a beneficial adaptation in the tumor-bearing mice, which eventually develop a reduction in cardiac wall thickness [2]. The increase in the amount of MHC-β was also associated with an increase in the amount of one of the apparent MHC-α fragments (MHC-α′) in tumor-bearing, which could also be an adaptation to maintain force generating ability with increased economy.…”

Section: Discussionmentioning

confidence: 99%

Losartan treatment attenuates tumor-induced myocardial dysfunction

Stevens

Velten²,

Youtz

et al. 2015

Journal of Molecular and Cellular Cardiology

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Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT)1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Methods and Results: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8 weeks of age. Simultaneously, mice were administered Losartan (10 mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19 days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. Conclusions: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation.

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“…In addition to the reduced Ca 2+ -transient amplitude, remodeling of contractile proteins, including altered expression of titin and myosin heavy chain isoforms, may contribute to AF-associated changes in atrial contractility [104,105] (Figure 3). Atrial contractility is also regulated by phosphorylation of contractile proteins, including the inhibitory troponin subunit (TnI), which influences Ca 2+ -sensitivity of the myofilaments and cMyBP-C, which determines Ca 2+ -sensitivity and kinetics of cross-bridge cycling [106].…”

Section: Altered Regulation Of Cardiac Electrophysiology and Contrmentioning

confidence: 99%

Serine/Threonine Phosphatases in Atrial Fibrillation

Heijman

Ghezelbash

Wehrens

et al. 2017

Journal of Molecular and Cellular Cardiology

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Serine/threonine protein phosphatases control dephosphorylation of numerous cardiac proteins, including a variety of ion channels and calcium-handling proteins, thereby providing precise post-translational regulation of cardiac electrophysiology and function. Accordingly, dysfunction of this regulation can contribute to the initiation, maintenance and progression of cardiac arrhythmias. Atrial fibrillation (AF) is the most common heart rhythm disorder and is characterized by electrical, autonomic, calcium-handling, contractile, and structural remodeling, which include, among other things, changes in the phosphorylation status of a wide range of proteins. Here, we review AF-associated alterations in the phosphorylation of atrial ion channels, calcium-handling and contractile proteins, and their role in AF-pathophysiology. We highlight the mechanisms controlling the phosphorylation of these proteins and focus on the role of altered dephosphorylation via local type-1, type-2A and type-2B phosphatases (PP1, PP2A, and PP2B, also known as calcineurin, respectively). Finally, we discuss the challenges for phosphatase research, potential therapeutic significance of altered phosphatase-mediated protein dephosphorylation in AF, as well as future directions.

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Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils

Cited by 44 publications

References 45 publications

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

Losartan treatment attenuates tumor-induced myocardial dysfunction

Serine/Threonine Phosphatases in Atrial Fibrillation

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