Altered β-adrenergic signal transduction in nonfailing hypertrophied myocytes from Dahl salt-sensitive rats

2000 ◽  
Vol 279 (5) ◽  
pp. H2502-H2508 ◽  
Author(s):  
Kohzo Nagata ◽  
Catherine Communal ◽  
Chee C. Lim ◽  
Mohit Jain ◽  
Thomas M. Suter ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Physiological Role ◽  
Cellular Level ◽  
Left Ventricular ◽  
Cell Shortening ◽  
Hypertrophied Myocardium ◽  
Intracellular Ca ◽  
Myocyte Contractility ◽  
Dose Dependent

Desensitization of the β-adrenergic receptor (β-AR) response is well documented in hypertrophied hearts. We investigated whether β-AR desensitization is also present at the cellular level in hypertrophied myocardium, as well as the physiological role of inhibitory G (Gi) proteins and the L-type Ca2+channel in mediating β-AR desensitization. Left ventricular (LV) myocytes were isolated from hypertrophied hearts of hypertensive Dahl salt-sensitive (DS) rats and nonhypertrophied hearts of normotensive salt-resistant (DR) rats. Cells were paced at a rate of 300 beats/min at 37°C, and myocyte contractility and intracellular Ca2+concentration ([Ca2+]i) were simultaneously measured. In response to increasing concentrations of isoproterenol, DR myocytes displayed a dose-dependent augmentation of cell shortening and the [Ca2+]i transient amplitude, whereas hypertrophied DS myocytes had a blunted response of both cell shortening and the [Ca2+]i transient amplitude. Interestingly, inhibition of Gi proteins did not restore β-AR desensitization in DS myocytes. The responses to increases in extracellular Ca2+ and an L-type Ca2+ channel agonist were also similar in both DS and DR myocytes. Isoproterenol-stimulated adenylyl cyclase activity, however, was blunted in hypertrophied myocytes. We concluded that compensated ventricular hypertrophy results in a blunted contractile response to β-AR stimulation, which is present at the cellular level and independent of alterations in inhibitory G proteins and the L-type Ca2+ channel.

scholarly journals Operative Myocardial protection in patients with Left Ventricular Hypertrophy: The Role of systemic Hypothermia

2011 ◽  
Vol 4 ◽  
pp. OJCS.S6937
Author(s):  
Tamer Elghobary ◽  
Idris M. Ali ◽  
Ahmad F. Ahmad
Keyword(s):  
Body Temperature ◽  
Myocardial Protection ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Group I ◽  
Hypertrophied Myocardium ◽  
Systemic Hypothermia ◽  
Group Ii ◽  
The Ideal

Objectives Myocardial hypertrophy represents a great challenge in cardiac surgery. Several strategies have been described to protect the hypertrophied myocardium during cardiopulmonary bypass, and aortic clamping, yet the ideal strategy has not been identified. This study investigates the use of moderate systemic hypothermia (MSH) as an adjuvant method to protect the hypertrophied myocardium in patients undergoing aortic valve replacement (AVR). Methods Twenty eight patients undergoing AVR were divided into two groups, (Group I) received continuous cold 5–8 °C retrograde blood cardioplegia (CRBC) and their body temperature was cooled down to 23–26 °C. (Group II) also received CRBC but their body temperature was kept at 32–34 °C. Results No operative morality (30 days) was noted in both groups. Postoperative reduction in ejection fraction (EF) was seen in nine patients of group I and in twelve patients of group II ( P < 0.05). The need for multiple inotropes was more in group II (eight patients) than in group I (two patients) ( P < 0.001). IABP was needed in three patients of group II and non in group I ( P < 0.01). Conclusion Moderate systemic hypothermia might have a role in protecting hypertrophied myocardium in patients undergoing AVR.

Abstract 313: STIM1 Silencing Reverses Pressure-overload Induced Cardiac Hypertrophy In Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ludovic O Bénard ◽  
Daniel S Matasic ◽  
Mathilde Keck ◽  
Anne-Marie Lompré ◽  
Roger J Hajjar ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Aortic Banding ◽  
Cross Section Area ◽  
Abdominal Aortic ◽  
Section Area

STromal Interaction Molecule 1 (STIM1), a membrane protein of the sarcoplasmic reticulum, has recently been proposed as a positive regulator of cardiomyocyte growth by promoting Ca2+ entry through the plasma membrane and the activation of Ca2+-mediated signaling pathways. We demonstrated that STIM1 silencing prevented the development of left ventricular hypertrophy (LVH) in rats after abdominal aortic banding. Our aim was to study the role of STIM1 during the transition from LVH to heart failure (HF). For experimental timeline, see figure. Transverse Aortic Constriction (TAC) was performed in C57Bl/6 mice. In vivo gene silencing was performed using recombinant Associated AdenoVirus 9 (AAV9). Mice were injected with saline or with AAV9 expressing shRNA control or against STIM1 (shSTIM1) (dose: 1e+11 viral genome), which decreased STIM1 cardiac expression by 70% compared to control. While cardiac parameters were similar between the TAC groups at weeks 3 and 6, shSTIM1 animals displayed a progressive and total reversion of LVH with LV walls thickness returning to values observed in sham mice at week 8. This reversion was associated with the development of significant LV dilation and severe contractile dysfunction, as assessed by echography. Hemodynamic analysis confirmed the altered contractile function and dilation of shSTIM1 animals. Immunohistochemistry showed a trend to more fibrosis. Despite hypertrophic stimuli, there was a significant reduction in cardiac myocytes cross-section area in shSTIM1-treated animals as compared to other TAC mice. This study showed that STIM1 is essential to maintain compensatory LVH and that its silencing accelerates the transition to HF.

Role of Calcineurin-Dependent Signaling Pathway on the Left Ventricular Hypertrophy Induced by Pressure Overload

2001 ◽  
Vol 31 (11) ◽  
pp. 1159
Author(s):  
Hainan Piao ◽  
Jin Sook Kwon ◽  
Hye Young Lee ◽  
Tae Jin Youn ◽  
Dong Woon Kim ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Signaling Pathway ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Dependent Signaling Pathway

Role of the cytoskeleton in rapid activation of CD11b/CD18 function and its subsequent downregulation in neutrophils

2000 ◽  
Vol 113 (15) ◽  
pp. 2737-2745
Author(s):  
S.I. Anderson ◽  
N.A. Hotchin ◽  
G.B. Nash
Keyword(s):  
Cytochalasin D ◽  
Calpain Inhibitor ◽  
Cytoskeletal Rearrangement ◽  
Activated Platelets ◽  
Binding Inhibition ◽  
Formyl Peptide ◽  
Intracellular Ca ◽  
Rapid Activation ◽  
Dose Dependent

When rolling adherent neutrophils are stimulated, they rapidly immobilize through activation of integrin CD11b/CD18, and then modulate attachment through this integrin to allow migration. We investigated links between cytoskeletal rearrangement and changes in function of integrin CD11b/CD18 in neutrophils stimulated with formyl peptide (fMLP). Neutrophils treated with the actin-polymerizing agent jasplakinolide became rolling adherent on monolayers of activated platelets, but could not use CD11b/CD18 to become immobilised when fMLP was perfused over them. If treated with jasplakinolide after fMLP, the cells stopped migrating but could not detach when fMLP was removed. Jasplakinolide did not inhibit changes in intracellular Ca(2+) seen after fMLP treatment, or inhibit neutrophil immobilisation induced by externally added Mn(2+). Thus cytoskeletal rearrangement was directly implicated in upregulation and, later, downregulation of CD11b/CD18 binding. Inhibition of RhoA with C3-transferase caused a dose-dependent reduction of initial rolling adhesion of neutrophils, and reduced the rate of migration after stimulation; however, neither the conversion of rolling to stationary adhesion, nor the ability of neutrophils to detach on removal of the stimulus, were inhibited. Thus, Rho may regulate actin polymerisation and motility in neutrophils, but did not appear to control integrin-mediated adhesion itself. Integrin binding may be promoted by disruption of links to the cytoskeleton, effected through depolymerisation of actin or cleavage of linking protein talin by calpain. Disruption of actin filaments with cytochalasin D did not, however, cause integrin-mediated immobilisation of rolling neutrophils. Although the calpain inhibitor calpeptin did inhibit the adhesion response to fMLP, this was only at doses where actin polymerisation was also ablated. We suggest that the cytoskeleton actively regulates binding conformation of CD11b/CD18 as well as its mobility in the membrane.

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