Talin and vinculin are downregulated in atherosclerotic plaque; Tampere Vascular Study.
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.



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.



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.



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.
BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland.
Magdaléna
M
von Essen
BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland.
Rolle
R
Rahikainen
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.
Niku
N
Oksala
Dep. of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
Emma
E
Raitoharju
Dep. of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
Ilkka
I
Seppälä
Heart Center, Tampere University Hospital, Tampere, Finland.
Ari
A
Mennander
Heart Center, Tampere University Hospital, Tampere, Finland.
Thanos
T
Sioris
Department of Pathology, Fimlab Laboratories, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
Ivana
I
Kholová
Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
Norman
N
Klopp
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.
Thomas
T
Illig
School of Medicine, University of Tampere and Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
Pekka J
PJ
Karhunen
Department of Clinical Physiology, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
Mika
M
Kähönen
Dep. of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
Terho
T
Lehtimäki
BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland. Electronic address: vesa.hytonen@uta.fi.
Vesa P
VP
Hytönen
D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000737:chemistry* / Q000473:pathology; D001018:Aortic Diseases / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000737:chemistry* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D021982:Cell-Matrix Junctions / Q000737:chemistry / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D005263:Femoral Artery / Q000737:chemistry* / Q000473:pathology; D005387:Finland; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000378:metabolism* / Q000473:pathology; D058226:Plaque, Atherosclerotic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D016608:Talin / Q000032:analysis* / Q000235:genetics; D066253:Vascular Remodeling; D016596:Vinculin / Q000032:analysis* / Q000235:genetics
D012333:RNA, Messenger; C518832:TLN1 protein, human; C436513:TLN2 protein, human; D016608:Talin; C488955:VCL protein, human; D016596:Vinculin
Atherosclerosis; Focal adhesion; Mechanobiology; Talin; Vinculin