268 - Molecular stabilizing mechanism in calcified carotid plaques (ID 610)
Abstract
Background and Aims
The molecular activity in calcified plaques and their clinical significance have not been fully clarified yet.
Methods
Carotid plaques from 28 endarterectomy patients were classified into high- and low-calcified plaques on the basis of calcium score (CaS). Twelve plaques were investigated for the alteration of gene expression by microarray analysis and qRT-PCR, and 6 other plaques underwent protein assessment. A microarray analysis for microRNA profiles was also performed, with validation by a miRNA qRT-PCR for another 10 plaques.
Results
Microarray analysis demonstrated 93 angiogenesis or growth factor–related transcripts. Among them, ANGPTL4 expression was significantly elevated, whereas FGFR2 expression was significantly suppressed. MRNA qRT-PCR was performed and augmented or decreased protein expression of each gene was confirmed by Western blotting analysis and immunohistochemistry. The miRNA microarray identified 697 probes. The expression of miRNA validated by qRT-PCR revealed a significant downregulation of hsa-miR-4530, hsa-miR133b, and hsa-miR-1-3p. A Spearman’s rank correlation analysis revealed that the logarithmic TGSs for the microarray of hsa-miR-4530 and hsa-miR-133b were significantly inversely correlated with the carotid plaques’ CaS, and the delta Cq values for the qRT-PCR showed a direct association.
Conclusions
In high-calcified plaques, ANGPTL4 might be upregulated for antiangiogenic modulating function together with the downregulation of FGFR2, contributing to the stability of the plaques. A specific profile for miRNA may also be identified, and the expressions of hsa-miR-4530 and hsa-miR-133b had inverse correlations with the CaS in the plaques, suggesting that miRNAs may play a modulating role in calcified plaques and plaque stability by targeting ANGPTL4 indicated with TargetScan algorithm.
