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4 results on '"Katarina Zihlavnikova Enayati"'

1. Inflammation and Mechanical Stress Stimulate Osteogenic Differentiation of Human Aortic Valve Interstitial Cells

Author

Maria Bogdanova, Aleksandra Kostina, Katarina Zihlavnikova Enayati, Arsenii Zabirnyk, Anna Malashicheva, Kåre-Olav Stensløkken, Gareth John Sullivan, Mari-Liis Kaljusto, John-Peder Escobar Kvitting, Anna Kostareva, Jarle Vaage, and Arkady Rutkovskiy

Subjects
inflammation, mechanical stress, valve interstitial cells, valve calcification, osteogenic differentiation, extracellular matrix, Physiology, QP1-981
Abstract

Background: Aortic valve calcification is an active proliferative process, where interstitial cells of the valve transform into either myofibroblasts or osteoblast-like cells causing valve deformation, thickening of cusps and finally stenosis. This process may be triggered by several factors including inflammation, mechanical stress or interaction of cells with certain components of extracellular matrix. The matrix is different on the two sides of the valve leaflets. We hypothesize that inflammation and mechanical stress stimulate osteogenic differentiation of human aortic valve interstitial cells (VICs) and this may depend on the side of the leaflet.Methods: Interstitial cells isolated from healthy and calcified human aortic valves were cultured on collagen or elastin coated plates with flexible bottoms, simulating the matrix on the aortic and ventricular side of the valve leaflets, respectively. The cells were subjected to 10% stretch at 1 Hz (FlexCell bioreactor) or treated with 0.1 μg/ml lipopolysaccharide, or both during 24 h. Gene expression of myofibroblast- and osteoblast-specific genes was analyzed by qPCR. VICs cultured in presence of osteogenic medium together with lipopolysaccharide, 10% stretch or both for 14 days were stained for calcification using Alizarin Red.Results: Treatment with lipopolysaccharide increased expression of osteogenic gene bone morphogenetic protein 2 (BMP2) (5-fold increase from control; p = 0.02) and decreased expression of mRNA of myofibroblastic markers: α-smooth muscle actin (ACTA2) (50% reduction from control; p = 0.0006) and calponin (CNN1) (80% reduction from control; p = 0.0001) when cells from calcified valves were cultured on collagen, but not on elastin. Mechanical stretch of VICs cultured on collagen augmented the effect of lipopolysaccharide. Expression of periostin (POSTN) was inhibited in cells from calcified donors after treatment with lipopolysaccharide on collagen (70% reduction from control, p = 0.001), but not on elastin. Lipopolysaccharide and stretch both enhanced the pro-calcific effect of osteogenic medium, further increasing the effect when combined for cells cultured on collagen, but not on elastin.Conclusion: Inflammation and mechanical stress trigger expression of osteogenic genes in VICs in a side-specific manner, while inhibiting the myofibroblastic pathway. Stretch and lipopolysaccharide synergistically increase calcification.

Published
2018
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2. Interstitial cells in calcified aortic valves have reduced differentiation potential and stem cell-like properties

Author

Anna Kostareva, Mari-Liis Kaljusto, Gareth J. Sullivan, Maria Bogdanova, Erik Dissen, Jarle Vaage, Katarina Zihlavnikova Enayati, Anna Malashicheva, Tommy A. Karlsen, Arkady Rutkovskiy, Arsenii Zabirnyk, Kåre-Olav Stensløkken, and John-Peder Escobar Kvitting

Subjects
Heart Defects, Congenital, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Contraction (grammar), Heart Valve Diseases, lcsh:Medicine, 030204 cardiovascular system & hematology, Article, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Bicuspid Aortic Valve Disease, Osteogenesis, medicine, Humans, lcsh:Science, Myofibroblasts, Cells, Cultured, Multidisciplinary, medicine.diagnostic_test, business.industry, Gene Expression Profiling, Stem Cells, lcsh:R, Calcinosis, Cell Differentiation, Aortic Valve Stenosis, Interstitial Cells of Cajal, Valvular disease, medicine.disease, Collagen gel, Osteogenic medium, Mechanisms of disease, 030104 developmental biology, Adipogenesis, Aortic Valve, lcsh:Q, Female, Aortic valve calcification, Stem cell, business, Biomarkers, Calcification
Abstract

Valve interstitial cells (VICs) are crucial in the development of calcific aortic valve disease. The purpose of the present investigation was to compare the phenotype, differentiation potential and stem cell-like properties of cells from calcified and healthy aortic valves. VICs were isolated from human healthy and calcified aortic valves. Calcification was induced with osteogenic medium. Unlike VICs from healthy valves, VICs from calcified valves cultured without osteogenic medium stained positively for calcium deposits with Alizarin Red confirming their calcific phenotype. Stimulation of VICs from calcified valves with osteogenic medium increased calcification (p = 0.02), but not significantly different from healthy VICs. When stimulated with myofibroblastic medium, VICs from calcified valves had lower expression of myofibroblastic markers, measured by flow cytometry and RT-qPCR, compared to healthy VICs. Contraction of collagen gel (a measure of myofibroblastic activity) was attenuated in cells from calcified valves (p = 0.04). Moreover, VICs from calcified valves, unlike cells from healthy valves had lower potential to differentiate into adipogenic pathway and lower expression of stem cell-associated markers CD106 (p = 0.04) and aldehyde dehydrogenase (p = 0.04). In conclusion, VICs from calcified aortic have reduced multipotency compared to cells from healthy valves, which should be considered when investigating possible medical treatments of aortic valve calcification.

Published
2019

3. Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans

Author

Arnt E. Fiane, Jarle Vaage, Arkady Rutkovskiy, Lars Gullestad, Håvard Attramadal, Julia Sagave, Christen P. Dahl, Vigdis Hillestad, Guro Valen, Shakil M Ahmed, Katarina Zihlavnikova Enayati, Gabor Czibik, Anton Baysa, and Jørgen Gravning

Subjects
0301 basic medicine, Adult, Cardiomyopathy, Dilated, Male, Pathology, medicine.medical_specialty, Clinical Biochemistry, Connective tissue, Bone Morphogenetic Protein 2, Coronary Artery Disease, 030204 cardiovascular system & hematology, Bone morphogenetic protein 2, Coronary artery disease, 03 medical and health sciences, Mice, 0302 clinical medicine, Left coronary artery, medicine.artery, Internal medicine, medicine, Animals, Humans, Bone morphogenetic protein receptor, Myocardial infarction, Coronary Artery Bypass, Bone Morphogenetic Protein Receptors, Type I, Aged, Heart Failure, business.industry, Myocardium, Connective Tissue Growth Factor, Dilated cardiomyopathy, General Medicine, Middle Aged, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Heart failure, Heart Function Tests, Cardiology, Female, business, Signal Transduction
Abstract

We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-infarction. Gene expression of bone morphogenetic protein receptor 1 beta was reduced in hearts of patients with failure, but increased two weeks following permanent ligation of the left coronary artery in mice. In conclusion, connective tissue growth factor is upregulated in hearts of humans with dilated cardiomyopathy, bone morphogenetic protein 2 is upregulated in remodeling due to myocardial infarction while its receptor 1 b in human failing hearts is downregulated. A potential explanation might be an attempt to engage regenerative processes, which should be addressed by further, mechanistic studies.

Published
2017

4. Interstitial Cells from Calcified and Healthy Aortic Valves Have Different Phenotype and Functions

Author

Kåre-Olav Stensløkken, Katarina Zihlavnikova Enayati, Arsenii Zabirnyk, Anna Malashicheva, Arkady Rutkovskiy, M. Bogdanova, and Jarle Vaage

Subjects
Aortic valve disease, Pathology, medicine.medical_specialty, business.industry, Medicine, Cardiology and Cardiovascular Medicine, business, Phenotype
Abstract

Objective: Valve interstitial cells (VICs) are crucial for the development of calcific aortic valve disease. We aimed to compare the phenotype and functions of VICs from calcified and healthy aorti...

Published
2019
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