Aims: Tet1, Tet2, and interleukin-6 (IL-6) have been linked to atherosclerosis. Whether Tet3 has a relationship with atherosclerosis and IL-6 was unknown. This study aims to determine the link between Tet3 and IL-6, and the role of Tet3 in prenatal hypoxia-induced atherosclerosis in offspring rats.
Main methods: Pregnant rats were divided into hypoxia and control group. Their male offspring were tested at 20 months old. Hematoxylin-eosin staining and transmission electron microscopic staining were used. Gene mRNA and protein levels were measured with q-PCR or Western blotting. Cell viability and migration was tested with MTT or cell scratch assay. 5-hmC and 5-mC expression were obtained by qGlucMS-PCR; 5-hmC and 5-mC activity were obtained by dot blotting.
Key findings: Chronic prenatal hypoxia increased Tet3 and IL-6 expression, and decreased Tet3 activity in offspring rats. GlucMS-qPCR showed the percentage of 5-hmC was significantly up-regulated in the promoter of IL-6 in both the rats and cells. Moreover, 5-hmC percentage also was increased in the A7r5 cells transfected with Tet3. Furthermore, Tet3 promoted proliferation and migration of A7r5 cells. However, Tet3 was not sensitive to acute hypoxia, while influenced by HIF-1α DNA element.
Significance: Tet3 enhanced IL-6 expression though up-regulating 5-hmC percentage in the IL-6 promoter.
Keywords: 5-hmC; Atherosclerosis; Hypoxia; IL-6; Tet3.
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