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- Krawczyk, Katarzyna
(författare)
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Transcriptional control in the vascular wall. Actin-responsive coactivators and smooth muscle transcripts.
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease (CVD) is the leading cause of death globally. In the European Union (EU) alone, CVD accounts for 1.8 million deaths each year. CVD is a group of disorders involving the heart and the blood vessels. The main risk factors of CVD include unhealthy lifestyles, tobacco smoking, and obesity. It has been demonstrated that chronic high blood pressure (medically termed hypertension) leads to serious clinical complications like myocardial infarction and stroke. Medical costs related to health care of CVD patients are estimated to €111 billion in the EU. It is well established that vascular smooth muscle cells (VSMCs) surrounding the blood vessels contribute to the development and progression of cardiovascular disease states. VSMCs are responsible for maintaining the vascular tone and for the regulation of blood flow and blood pressure. VSMCs are characterized by a high plasticity, which enables them to modulate their phenotype in response to intracellular and extracellular stimuli, like shear stress, high blood pressure, and hormones. VSMCs can adopt a de-differentiated, synthetic phenotype, which is associated with altered expression of many smooth muscle proteins involved in the contraction-relaxation process. The ability of VSMCs to modulate their phenotype is also termed phenotypic switching. The synthetic, proliferative VSMCs are essential during the development of vessels and in wound healing processes, whereas in adult blood vessels, most VSMCs exhibit a differentiated, quiescent phenotype. Many studies have demonstrated the contribution of dedifferentiated SMCs to maladaptive arterial remodelling. Hence, understanding the molecular mechanisms involved in phenotypic modulation of VSMCs is crucial to improve global health. The main aim of this thesis was to unravel new molecular mechanisms underlying phenotypic modulation of VSMCs. Here, I demonstrate what is likely to be a major regulatory mechanism for biogenesis of caveolae, which are small membrane organelles typical of contractile and quiescent VSMCs. I find that the expression of caveolin and cavin genes is regulated by two members of the myocardin-related transcription factors: MYOCD and MRTF-A. In the second study, we show that Notch signalling impairment decreases the expression of soluble guanylyl cyclase in VSMCs in hypertension. In my third study, I show that the expression of endothelin type B receptors is controlled by MRTF-B, ELK1, and actin cytoskeletal dynamics. In my last study, finally, synemin is identified as a new target of myocardin-related transcription factors in VSMCs. Taken together, the findings in this thesis expand the knowledge of transcriptional control mechanisms and physiology of vascular smooth muscle. Such understanding is likely to be essential for the development of new effective strategies for the prevention and treatment of cardiovascular disease.
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| 2. |
- Krawczyk, M, et al.
(författare)
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Electronic and hole minibands in quantum wire arrays of different crystallographic structure
- 2010
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Ingår i: PHYSICS LETTERS A. - : Elsevier BV. - 0375-9601. ; 374:4, s. 647-654
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Tidskriftsartikel (refereegranskat)abstract
- We consider semiconductor heterostructures consisting of GaAs rods embedded in AlxGa1-xAs and disposed in sites of a Square or triangular lattice. The electronic and hole spectra around the conduction band bottom and the valence band top are examined for electrons and holes propagating in plane of periodicity, versus geometry of the lattice formed by the rods, concentration of At in the matrix material, and structural parameters including the filling fraction and the lattice constant. Our calculations use the envelope function and are based on the effective-mass approximation. We show that the electronic and hole spectra resulting from the periodicity of the heterostructure, depend on the factors considered and that the effect of lattice geometry varies substantially with lattice constant. For low lattice constant values the minigaps are significantly wider in the case of triangular lattice, while for high lattice constant values only slightly thiner minigaps Occur in the Square lattice-based arrays. We discuss the consequences of our findings for the efficiency of solar cells.
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