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Myofilament Ca2+ sensitivity correlates with left ventricular contractility during the progression of pressure overload-induced left ventricular myocardial hypertrophy in rats

Aim - Here we aimed at investigating the relation between left ventricular (LV) contractility and myofilament function during the development and progression of pressure overload (PO)-induced LV myocardial hypertrophy (LVH). - Methods - Abdominal aortic banding (AB) was performed to induce PO in rat...

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Main Authors: Ruppert, Mihály (Author) , Korkmaz-İçöz, Sevil (Author) , Loganathan, Sivakkanan (Author) , Lehmann, Lorenz (Author) , Sayour, Alex Ali (Author) , Karck, Matthias (Author) , Szabó, Gábor (Author)
Format: Article (Journal)
Language:English
Published: 4 March 2019
In: Journal of molecular and cellular cardiology
Year: 2019, Volume: 129, Pages: 208-218
ISSN:1095-8584
DOI:10.1016/j.yjmcc.2019.02.017
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.yjmcc.2019.02.017
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0022282818312860
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Author Notes:Mihály Ruppert, Beáta Bódi, Sevil Korkmaz-Icöz, Sivakkanan Loganathan, Weipeng Jiang, Lorenz Lehmann, Attila Oláh, Bálint András Barta, Alex Ali Sayour, Béla Merkely, Matthias Karck, Zoltán Papp, Gábor Szabó, Tamás Radovits
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Summary:Aim - Here we aimed at investigating the relation between left ventricular (LV) contractility and myofilament function during the development and progression of pressure overload (PO)-induced LV myocardial hypertrophy (LVH). - Methods - Abdominal aortic banding (AB) was performed to induce PO in rats for 6, 12 and 18weeks. Sham operated animals served as controls. Structural and molecular alterations were investigated by serial echocardiography, histology, quantitative real-time PCR and western blot. LV function was assessed by pressure-volume analysis. Force measurement was carried out in permeabilized cardiomyocytes. - Results - AB resulted in the development of pathological LVH as indicated by increased heart weight-to-tibial length ratio, LV mass index, cardiomyocyte diameter and fetal gene expression. These alterations were already present at early stage of LVH (AB-week6). Furthermore, at more advanced stages (AB-week12, AB-week18), myocardial fibrosis and chamber dilatation were also observed. From a hemodynamic point of view, the AB-wk6 group was associated with increased LV contractility, maintained ventriculo-arterial coupling (VAC) and preserved systolic function. In the same experimental group, increased myofilament Ca2+ sensitivity (pCa50) and hyperphosphorylation of cardiac troponin-I (cTnI) at Threonine-144 was detected. In contrast, in the AB-wk12 and AB-wk18 groups, the initial augmentation of LV contractility, as well as the increased myofilament Ca2+ sensitivity and cTnI (Threonine-144) hyperphosphorylation diminished, leading to impaired VAC and reduced systolic performance. Strong correlation was found between LV contractility parameters and myofilament Ca2+-sensitivity among the study groups. - Conclusion - Changes in myofilament Ca2+ sensitivity might underlie the alterations in LV contractility during the development and progression of PO-induced LVH.
Item Description:Im Titel ist 2+ hochgestellt
Gesehen am 24.03.2020
Physical Description:Online Resource
ISSN:1095-8584
DOI:10.1016/j.yjmcc.2019.02.017

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