Identification of transcription factors and gene clusters in rabbit smooth muscle cells during high flow-induced vascular remodeling via microarray

• ECM-related genes are enriched during high flow-induced vascular remodeling.
• Metabolic and immune function-related pathways result in vascular remodeling.
• SMCs exhibit 25 differentially expressed TFs in response to hemodynamic stress.
• FOXN4 regulates the promoter activity of MMP2 and MMP9.

ABSTRACTSustained blood flow, especially high blood flow causes the remodeling of arteries. The molecular mechanism of vascular remodeling has been mainly investigated in cultured cells. However, the in vivo molecular mechanism is poorly understood. In this study, we performed microarray analysis to explore the gene expression profile of smooth muscle cells (SMCs) during vascular remodeling. Transcriptional profiles indicated that 947 genes were differentially expressed in SMCs responding to high flow compared with the sham control, of which 617 genes were up-regulated and 330 genes were down-regulated. Gene ontology analysis revealed the special participation of extracellular matrix related genes during high flow-induced vascular remodeling. KEGG pathway analysis showed the enrichment of metabolism and immune function associated genes in SMCs exposed to high flow. Besides, we also identified 25 differentially expressed transcription factors potentially impacted by hemodynamic insult. Finally, we revealed FOXN4 as a novel transcription factor that could modulate MMP2 and MMP9 transcriptional activity. Collectively, our results revealed major gene clusters and transcription factors in SMCs during vascular remodeling which may provide an insight into the molecular mechanism of vascular remodeling and facilitate the screening of candidate genes for vascular diseases.