Magdaléna von Essen1, Rolle Rahikainen1, Niku Oksala2, Emma Raitoharju3, Ilkka Seppälä3, Ari Mennander4, Thanos Sioris4, Ivana Kholová5, Norman Klopp6, Thomas Illig7, Pekka J Karhunen8, Mika Kähönen9, Terho Lehtimäki3, Vesa P Hytönen10. 1. BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland. 2. Dep. of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland; Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland. 3. Dep. of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland. 4. Heart Center, Tampere University Hospital, Tampere, Finland. 5. Department of Pathology, Fimlab Laboratories, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland. 6. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany. 7. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany; Institute of Human Genetics, Hannover Medical School, Hannover, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 8. School of Medicine, University of Tampere and Fimlab Laboratories, Tampere University Hospital, Tampere, Finland. 9. Department of Clinical Physiology, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland. 10. BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland. Electronic address: vesa.hytonen@uta.fi.
Abstract
BACKGROUND AND AIMS: Focal adhesions (FA) play an important role in the tissue remodeling and in the maintenance of tissue integrity and homeostasis. Talin and vinculin proteins are among the major constituents of FAs contributing to cellular well-being and intercellular communication. METHODS: Microarray analysis (MA) and qRT-PCR low-density array were implemented to analyze talin-1, talin-2, meta-vinculin and vinculin gene expression in circulating blood and arterial plaque. RESULTS: All analyzed genes were significantly and consistently downregulated in plaques (carotid, abdominal aortic and femoral regions) compared to left internal thoracic artery (LITA) control. The use of LITA samples as controls for arterial plaque samples was validated using immunohistochemistry by comparing LITA samples with healthy arterial samples from a cadaver. Even though the differences in expression levels between stable and unstable plaques were not statistically significant, we observed further negative tendency in the expression in unstable atherosclerotic plaques. The confocal tissue imaging revealed gradient of talin-1 expression in plaque with reduction close to the vessel lumen. Similar gradient was observed for talin-2 expression in LITA controls but was not detected in plaques. This suggests that impaired tissue mechanostability affects the tissue remodeling and healing capabilities leading to development of unstable plaques. CONCLUSIONS: The central role of talin and vinculin in cell adhesions suggests that the disintegration of the tissue in atherosclerosis could be partially driven by downregulation of these genes, leading to loosening of cell-ECM interactions and remodeling of the tissue. Copyright Â
BACKGROUND AND AIMS: Focal adhesions (FA) play an important role in the tissue remodeling and in the maintenance of tissue integrity and homeostasis. Talin and vinculin proteins are among the major constituents of FAs contributing to cellular well-being and intercellular communication. METHODS: Microarray analysis (MA) and qRT-PCR low-density array were implemented to analyze talin-1, talin-2, meta-vinculin and vinculin gene expression in circulating blood and arterial plaque. RESULTS: All analyzed genes were significantly and consistently downregulated in plaques (carotid, abdominal aortic and femoral regions) compared to left internal thoracic artery (LITA) control. The use of LITA samples as controls for arterial plaque samples was validated using immunohistochemistry by comparing LITA samples with healthy arterial samples from a cadaver. Even though the differences in expression levels between stable and unstable plaques were not statistically significant, we observed further negative tendency in the expression in unstable atherosclerotic plaques. The confocal tissue imaging revealed gradient of talin-1 expression in plaque with reduction close to the vessel lumen. Similar gradient was observed for talin-2 expression in LITA controls but was not detected in plaques. This suggests that impaired tissue mechanostability affects the tissue remodeling and healing capabilities leading to development of unstable plaques. CONCLUSIONS: The central role of talin and vinculin in cell adhesions suggests that the disintegration of the tissue in atherosclerosis could be partially driven by downregulation of these genes, leading to loosening of cell-ECM interactions and remodeling of the tissue. Copyright Â
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