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




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



Autor: Teresa Palao, Karl Swärd, Aldo Jongejan, Perry D. Moerland, Judith de Vos, Angela van Weert, Silvia M. Arribas, Gergely Groma, E

Fuente: http://plos.srce.hr/



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