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Talin and vinculin are downregulated in atherosclerotic plaque; Tampere Vascular Study
Magdaléna von Essen1, Rolle Rahikainen1, Niku Oksala2
1BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland.
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.
Insights
Gene expression of talin and vinculin proteins, crucial for focal adhesions (FA), is downregulated in atherosclerotic plaques. This suggests impaired cell-matrix interactions contribute to tissue disintegration in atherosclerosis.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Cell Biology
Background:
- Focal adhesions (FA) are critical for tissue remodeling, integrity, and homeostasis.
- Talin and vinculin are key proteins in FA, supporting cellular functions and communication.
Purpose of the Study:
- To investigate the gene expression of talin-1, talin-2, meta-vinculin, and vinculin in circulating blood and arterial plaques.
- To correlate gene expression levels with the stability of atherosclerotic plaques.
Main Methods:
- Microarray analysis (MA) and qRT-PCR low-density array were used for gene expression analysis.
- Immunohistochemistry validated the use of Left Internal Thoracic Artery (LITA) as a control for arterial plaque samples.
- Confocal tissue imaging was employed to visualize protein expression gradients.
Main Results:
- Talin-1, talin-2, meta-vinculin, and vinculin genes were significantly downregulated in carotid, abdominal aortic, and femoral plaques compared to LITA controls.
- A trend towards further downregulation was observed in unstable atherosclerotic plaques.
- Talin-1 expression showed a gradient in plaques, decreasing towards the lumen, while talin-2 showed a gradient in LITA controls but not in plaques.
Conclusions:
- Downregulation of talin and vinculin in atherosclerosis may contribute to tissue disintegration by weakening cell-extracellular matrix interactions.
- Impaired tissue mechanostability, indicated by altered protein expression, may promote the development of unstable plaques.