Gene Expression and MicroRNA Expression Analysis in Small Arteries of Spontaneously Hypertensive Rats. Evidence for ER Stress

• DOI: 10.1371/journal.pone.0137027
• Publication Date: 2015-09-10T17:58:37Z
• Authors: Teresa Palao; Karl Swärd; Aldo Jongejan; Perry D. Moerland; Judith de Vos; Angela van Weert; Silvia M. Arribas; Gergely Groma; Ed vanBavel; Erik N. T. P. Bakker
• Keywords: ATF6; Mesenteric arteries; Spontaneously hypertensive rat; XBP1

Small arteries are known to develop functional and structural alterations in hypertension. However, the mechanisms of this remodeling not fully understood. We hypothesized that altered gene expression is associated with development hypertension mesenteric spontaneously hypertensive rats (SHR). Three sublines SHR normotensive Wistar Kyoto (WKY) were studied at 6 weeks 5 months age. MiRNA mRNA microarray experiments performed analyzed bioinformatical tools, including Ingenuity Pathway Analysis (IPA). Principal component analysis showed a clear separation both miRNA levels between ages studied, demonstrating strong age-related changes expression. At level, IPA identified differences WKY related metabolic diseases, cellular growth, proliferation. The mRNAs differentially expressed metabolism, movement most strongly upregulated (9.2-fold) was thrombospondin 4 (Thbs4), protein involved endoplasmic reticulum (ER) stress response activates transcription factor 6α (ATF6α). ATF6α downstream targets also vs. WKY. Differential THBS4, cleaved form ATF6α, two its further confirmed level by western blot. In summary, these data revealed number genes (n = 202) miRNAs 3) had been previously. prominent these, Thbs4, vascular ER