Vascular Transcriptome Profiling Reveals Aging-Related Genes in Angiotensin Ⅱ-Induced Hypertensive Mouse Aortas

摘要

Objective AngiotensinⅡ(AngⅡ)-induced vascular damage is a major risk of hypertension.However,the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear.In this study,we explored the novel mechanism associated with Ang Il-induced hypertension.Methods We treated 8-to 12-week-old C57BL/6J male mice with saline and AngⅡ(0.72 mg/kg-d)for 28 days,respectively.Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing.Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot.Functional annotations including Gene Ontology(GO)and Koto Encyclopedia of Genes and Genomes(KEGG)pathway were performed to reveal the molecular mechanism of AngⅡ-induced hypertension.Finally,the differentially expressed genes were validated by using quantitative real-time PCR.Results The result revealed that a total of 773 genes,including 599 up-regulated genes and 174 down-regulated genes,were differentially expressed in the aorta of AngⅡ-induced hypertension mice model.Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the AngⅡ-induced hypertension,including some pathways associated with hypertension such as extracellular matrix,inflammation and immune response.Interestingly,we also found that the differentially expressed genes were enriched in vascular aging pathway,and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased(P<0.05).Conclusion We identify that vascular aging is involved in AngⅡ-induced hypertension,and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.