scholarly journals Vinculin network–mediated cytoskeletal remodeling regulates contractile function in the aging heart

2015 ◽  
Vol 7 (292) ◽  
pp. 292ra99-292ra99 ◽  
Author(s):  
Gaurav Kaushik ◽  
Alice Spenlehauer ◽  
Ayla O. Sessions ◽  
Adriana S. Trujillo ◽  
Alexander Fuhrmann ◽  
...  
2008 ◽  
Vol 294 (5) ◽  
pp. H2174-H2183 ◽  
Author(s):  
J. Darcy O'Brien ◽  
Jessica H. Ferguson ◽  
Susan E. Howlett

This study examined the impact of age on contractile function, Ca2+ homeostasis, and cell viability in isolated myocytes exposed to simulated ischemia and reperfusion. Ventricular myocytes were isolated from anesthetized young adult (3 mo) and aged (24 mo) male Fischer 344 rats. Cells were field-stimulated at 4 Hz (37°C), exposed to simulated ischemia, and reperfused with Tyrode solution. Cell shortening and intracellular Ca2+ were measured simultaneously with an edge detector and fura-2. Cell viability was assessed by Trypan blue exclusion. Ischemia (20–45 min) depressed amplitudes of contraction equally in isolated myocytes from young adult and aged animals. The degree of postischemic contractile depression (stunning) was comparable in both groups. Ca2+ transient amplitudes were depressed in early reperfusion in young adult and aged cells and then recovered to preischemic levels in both groups. Cell viability also declined equally in reperfusion in both groups. In short, some cellular responses to simulated ischemia and reperfusion were similar in both groups. Even so, aged myocytes exhibited a much greater and more prolonged accumulation of diastolic Ca2+ in ischemia and in early reperfusion compared with myocytes from younger animals. In addition, the degree of mechanical alternans in ischemia increased significantly with age. The observation that there is an age-related increase in accumulation of diastolic Ca2+ in ischemia and early reperfusion may account for the increased sensitivity to ischemia and reperfusion injury in the aging heart. The occurrence of mechanical alternans in ischemia may contribute to contractile dysfunction in ischemia in the aging heart.


2014 ◽  
Vol 106 (2) ◽  
pp. 778a
Author(s):  
Gaurav Kaushik ◽  
Alice Spenlehauer ◽  
Ayla Sessions ◽  
Danielle Pohl ◽  
Adriana Trujillo ◽  
...  

2021 ◽  
Vol 22 (19) ◽  
pp. 10293
Author(s):  
Evelin Major ◽  
Ilka Keller ◽  
Dániel Horváth ◽  
István Tamás ◽  
Ferenc Erdődi ◽  
...  

The pathological elevation of the active thyroid hormone (T3) level results in the manifestation of hyperthyroidism, which is associated with alterations in the differentiation and contractile function of skeletal muscle (SKM). Myosin phosphatase (MP) is a major cellular regulator that hydrolyzes the phosphoserine of phosphorylated myosin II light chain. MP consists of an MYPT1/2 regulatory and a protein phosphatase 1 catalytic subunit. Smoothelin-like protein 1 (SMTNL1) is known to inhibit MP by directly binding to MP as well as by suppressing the expression of MYPT1 at the transcriptional level. Supraphysiological vs. physiological concentration of T3 were applied on C2C12 myoblasts and differentiated myotubes in combination with the overexpression of SMTNL1 to assess the role and regulation of MP under these conditions. In non-differentiated myoblasts, MP included MYPT1 in the holoenzyme complex and its expression and activity was regulated by SMTNL1, affecting the phosphorylation level of MLC20 assessed using semi-quantitative Western blot analysis. SMTNL1 negatively influenced the migration and cytoskeletal remodeling of myoblasts measured by high content screening. In contrast, in myotubes, the expression of MYPT2 but not MYPT1 increased in a T3-dependent and SMTNL1-independent manner. T3 treatment combined with SMTNL1 overexpression impeded the activity of MP. In addition, MP interacted with Na+/K+-ATPase and dephosphorylated its inhibitory phosphorylation sites, identifying this protein as a novel MP substrate. These findings may help us gain a better understanding of myopathy, muscle weakness and the disorder of muscle regeneration in hyperthyroid patients.


1996 ◽  
Vol 35 (05) ◽  
pp. 146-152 ◽  
Author(s):  
A. Kögler ◽  
H.-A. Schmitt ◽  
D. Emrich ◽  
H. Kreuzer ◽  
D. L. Munz ◽  
...  

SummaryThis prospective study assessed myocardial viability in 30 patients with coronary heart disease and persistent defects despite reinjection on TI-201 single-photon computed tomography (SPECT). In each patient, three observers graded TI-201 uptake in 7 left ventricular wall segments. Gradient-echo magnetic resonance imaging in the region of the persistent defect generated 12 to 16 short axis views representing a cardiac cycle. A total of 120 segments were analyzed. Mean end-diastolic wall thickness and systolic wall thickening (± SD) was 11.5 ± 2.7 mm and 5.8 ± 3.9 mm in 48 segments with normal TI-201 uptake, 10.1 ± 3.4 mm and 3.7 ± 3.1 mm in 31 with reversible lesions, 11.3 ± 2.8 mm and 3.3 ± 1.9 mm in 10 with mild persistent defects, 9.2 ± 2.9 mm and 3.2 ±2.2 mm in 15 with moderate persistent defects, 5.8 ± 1.7 mm and 1.3 ± 1.4 mm in 16 with severe persistent defects, respectively. Significant differences in mean end-diastolic wall thickness (p <0.0005) and systolic wall thickening (p <0.005) were found only between segments with severe persistent defects and all other groups, but not among the other groups. On follow-up in 11 patients after revascularization, 6 segments with mild-to-moderate persistent defects showed improvement in mean systolic wall thickening that was not seen in 6 other segments with severe persistent defects. These data indicate that most myocardial segments with mild and moderate persistent TI-201 defects after reinjection still contain viable tissue. Segments with severe persistent defects, however, represent predominantly nonviable myocardium without contractile function.


2016 ◽  
pp. 46-51
Author(s):  
T. Dermenzhy ◽  
◽  
V. Svintitskiy ◽  
S. Nespryadko ◽  
L. Legerda ◽  
...  

The objective: to improve an effectiveness of therapy and quality of life of patients with infiltrative cervical cancer using radical hysterectomy accomplished with nerve-sparing methodology. Patients and Methods: Ninety patients with histologically verified infiltrative cervical cancer were cured with radical hysterectomy (RHE) in the Department of Oncogynecology of National Cancer Institute (Kyiv, Ukraine) in 2012-2016. The age of the patients was from 26 to 65 years (an average age of 42.61±1.06). The patients were distributed in 2 groups: group I treated with nerve-sparing radical hysterectomy (NSRHE), 45 patients, the main group; group II treated with radical hysterectomy (RHE III), the control group, 45 patients. The prognostic indexes in the groups were similar. Results. NSRHE that included the dissection of cardinal ligament, separation of dorsal and anterior layers of uterovesical ligament allowed separate uterine branch of inferior hypogastric plexus, preserve an innervation of urinary bladder and prevent the malfunction of its contractile function at postoperative period. Conclusion. The data of the urodynamic study using cystomanometry performed at pre- and early operative periods have shown that surgical treatment of patients with infiltrative cervical cancer with preservation of the major elements of pelvic autonomic plexuses allows significantly decrease the rate of postoperative urogenical malfunctions. Key words: nerve-sparing radical hysterectomy, cervical cancer, cystomanometry.


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