Sox9 is increased in arterial plaque and stenosis, associated with synthetic phenotype of vascular smooth muscle cells and causes alterations in extracellular matrix and calcification

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Augstein, Antje¹  Mierke, Johannes¹  Poitz, David M.^1,2  Strasser, Ruth H.¹ 

[1] Tech Univ Dresden, Heart Ctr Dresden, Internal Med & Cardiol, Dresden, Germany

[2] Tech Univ Dresden, Inst Clin Chem & Lab Med, Dresden, Germany

关键词: Arteriosclerosis;    smooth muscle cells;    Phenotypic switch;    Extracellular matrix;    Calcification;   

DOI  :  10.1016/j.bbadis.2018.05.009

来源: Elsevier

【 摘 要 】

Vascular smooth muscle cells (VSMC) exhibit a dual role in progression and maintenance of arteriosclerosis. They are fundamental for plaque stability but also can drive plaque progression. During pathogenic vascular remodeling, VSMC transdifferentiate into a phenotype with enhanced proliferation and migration. Moreover, they exert an increased capacity to generate extracellular matrix proteins. A special lineage of transdifferentiated VSMC expresses Sox9, a multi-functional transcription factor. The aim of the study was to examine the role of Sox9 in phenotypic alterations leading to arteriosclerosis. Using mouse models for arterial stenosis, Sox9 induction in diseased vessels was verified. The phenotypic switch of VSMC from contractile to proliferative nature caused a significant increase of Sox9 expression. Various factors known to be involved in the progression of arteriosclerosis were examined for their ability to modulate Sox9 expression in VSMC. While PDGF-BB resulted in a strong transient upregulation of Sox9, TGF-beta 1 appeared to be responsible for a moderate, but prolonged increase of Sox9 expression. Beside the regulation, functional studies focused on knockout and overexpression of Sox9. A Sox9-dependent alteration of extracellular matrix could be revealed and was associated with an upregulated calcium deposition. Taken together, Sox9 is identified as important factor of VSMC function by modulation the extracellular matrix composition and calcium deposition, which are important processes in plaque development.

【 授权许可】

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