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Excitation-Contraction and Excitation-Transcription Coupling in Vascular Smooth Muscle Cells: Alterations in Experimental Hypertension and Vascular Remodeling
Misárková, Eliška ; Zicha, Josef (advisor) ; Hock, Miroslav (referee)
Vascular smooth muscle cells (VSMCs) express considerable phenotype plasticity. They are able to change their phenotype in vivo if necessary. It is important to know that during this phenotype switch the expression of transport proteins and channels is modified, which results in significant alteration of Ca2+ signaling in smooth muscle cells. In differentiated cells, which represent contractile phenotype, there are dominant rapid, transient events in intracellular Ca2+ concentration (Ca2+ i), while the resting cytosolic Ca2+ i concentration is low. In differentiated cells these Ca2+ i events are mainly caused by two components of the Ca2+ signalling pathways: 1) extracellular Ca2+ influx via L-type voltage-gated Ca2+ channels (L-type VGCC) in plasma membrane, and 2) depletion of intracellular Ca2+ stores via ryanodin receptors located on sarcoplasmic reticulum. Rapid Ca2+ i oscillations are quickly reduced by numerous Ca2+ ATPases of sarco/endoplasmic reticulum and plasma membrane. Proliferating vascular smooth muscle cells are characterized by a long-lasting Ca2+ i oscillations accompanied by sustained elevation of basal intracellular Ca2+ concentration. During phenotype switch from contractile phenotype to proliferative phenotype there is decreased Ca2+ ATPase activity, and store-operated Ca2+...
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Phenotypic plasticity of smooth muscle cells
Misárková, Eliška ; Zicha, Josef (advisor) ; Pácha, Jiří (referee)
Vascular smooth muscle cells display a certain level of phenotype plasticity. Under specific conditions fully differentiated cells are able to undergo dedifferentiation and to restart growth and proliferation. An organ culture method is a useful technique for the analysis of dedifferentiation of vascular smooth muscle cells, because it provides an opportunity for studying the changes in cell phenotype. The aim of this study was to investigate the basic contractile characteristics in rat femoral arteries cultured for different time periods (from one to three days). In addition, the effects of fetal bovine serum (FBS), that contains various growth factors and other biological active molecules, on contractile function were studied. We also tried to attenuate cell dedifferentiation by lowering the calcium influx, because calcium is an important second messenger participating in cell growth and proliferation. To achieve this goal we used cultivation with nifedipine, a voltage-dependent calcium channel inhibitor. The cultivation without FBS slightly decreased arterial contractility, whereas the cultivation with FBS decreased arterial contractility considerably. The major change in contractility of arteries cultivated with FBS occurred approximately within 24 hours of cultivation. The cultivation with...
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Excitation-Contraction and Excitation-Transcription Coupling in Vascular Smooth Muscle Cells: Alterations in Experimental Hypertension and Vascular Remodeling
Misárková, Eliška ; Zicha, Josef (advisor) ; Hock, Miroslav (referee)
Vascular smooth muscle cells (VSMCs) express considerable phenotype plasticity. They are able to change their phenotype in vivo if necessary. It is important to know that during this phenotype switch the expression of transport proteins and channels is modified, which results in significant alteration of Ca2+ signaling in smooth muscle cells. In differentiated cells, which represent contractile phenotype, there are dominant rapid, transient events in intracellular Ca2+ concentration (Ca2+ i), while the resting cytosolic Ca2+ i concentration is low. In differentiated cells these Ca2+ i events are mainly caused by two components of the Ca2+ signalling pathways: 1) extracellular Ca2+ influx via L-type voltage-gated Ca2+ channels (L-type VGCC) in plasma membrane, and 2) depletion of intracellular Ca2+ stores via ryanodin receptors located on sarcoplasmic reticulum. Rapid Ca2+ i oscillations are quickly reduced by numerous Ca2+ ATPases of sarco/endoplasmic reticulum and plasma membrane. Proliferating vascular smooth muscle cells are characterized by a long-lasting Ca2+ i oscillations accompanied by sustained elevation of basal intracellular Ca2+ concentration. During phenotype switch from contractile phenotype to proliferative phenotype there is decreased Ca2+ ATPase activity, and store-operated Ca2+...
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