Background
Carotid plaques with expansive arterial remodeling are closely related to cerebral ischemic events. Although S100A4 (S100 calcium‐binding protein A4) is expressed in atherosclerotic lesions, its role in atherosclerotic plaque progression remains unknown. In this study, we examined the association between carotid arterial expansive remodeling and S100A4 expression.
Methods and Results
Preoperative high‐resolution magnetic resonance imaging was used to assess luminal stenosis and vascular remodeling in patients undergoing carotid endarterectomy. To examine murine carotid atherosclerosis, we induced experimental lesions by flow cessation in apolipoprotein E‐deficient mice fed a high‐fat diet. The role of S100A4 in plaque formation and smooth muscle cell proliferation was investigated in vivo and in vitro, respectively. Human carotid arterial expansive remodeling showed positive correlations with the expression of
S100A4
,
MMP2
, and
MMP9
.
S100A4
mRNA levels were positively correlated with those of
MMP2
,
MMP9
, and
MMP13
. S100A4 was expressed in vascular smooth muscle cells (VSMCs) and VSMC‐derived foam cells in the plaque shoulder and marginal areas. S100A4 expression increased concomitantly with plaque formation in our animal model. Exogenous recombinant S100A4 protein enhanced the levels of
Mmp2
,
Mmp9
, and
Mmp13
and the cell proliferation ability in VSMCs. A chemotaxis assay indicated that extracellular S100A4 functions as a chemoattractant for VSMCs.
Conclusions
S100A4 expression was elevated in human carotid plaques and showed a positive correlation with the degree of expansive remodeling. S100A4‐positive VSMC‐derived cells are considered to play an important role in carotid expansive remodeling.
Increased expression of calcium-binding protein S100 in human uterine smooth muscle tumours
