Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Sep 7;12(9):e0184233.
doi: 10.1371/journal.pone.0184233. eCollection 2017.

Cerebrovascular gene expression in spontaneously hypertensive rats

Anne-Sofie Grell  1 , Simona Denise Frederiksen  1 , Lars Edvinsson  1   2 , Saema Ansar  2
Affiliations

Cerebrovascular gene expression in spontaneously hypertensive rats

Anne-Sofie Grell et al. PLoS One. .

Abstract

Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for vascular diseases such as stroke. Blood vessels exposed to chronic shear stress develop structural changes and remodeling of the vascular wall through many complex mechanisms. However, the molecular mechanisms involved are not fully understood. Hypertension-susceptible genes may provide a novel insight into potential molecular mechanisms of hypertension and secondary complications associated with hypertension. The aim of this exploratory study was to identify gene expression differences in the middle cerebral arteries between 12-week-old male spontaneously hypertensive rats and their normotensive Wistar-Kyoto rats using an Affymetrix whole-transcriptome expression profiling. Quantitative PCR and western blotting were used to verify genes of interest. 169 genes were differentially expressed in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Serpine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion, the identified genes in the middle cerebral arteries from spontaneously hypertensive rats could be possible mediators of the vascular changes and secondary complications associated with hypertension. This study supports the selection of key genes to investigate in the future research of hypertension-induced end-organ damage.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. GO overrepresentation analysis network.
Network of the differentially expressed genes (q = 0) in the MCAs from SHRs (n = 5) compared to WKY rats (n = 5).
Fig 2
Fig 2. Volcano plot.
Red and blue dots are differentially expressed genes (q = 0) in the MCAs from SHRs (n = 5) compared to WKY rats (n = 5). Red dots are genes verified by qPCR.
Fig 3
Fig 3. Heat map of genes verified by qPCR.
Box color and color key show the expression level differences between WKY rats (n = 5) and SHRs (n = 5), reported as the Z score, which is the scaled gene expression measurement (scaled row-wise, mean = 0, SD = 1). As expected, WKY rats and SHRs are grouped separately due to distinct expression patterns between groups. The numbers in the boxes represent normalized expression values of each gene for each rat.
Fig 4
Fig 4. LOX1 protein level.
LOX1 (also known as OLR1) expression in the cerebral arteries from SHRs compared to WKY rats and representative blot of LOX1 and β-ACTIN. Data is normalized to Jurkat cells and β-ACTIN. Data is expressed as median ± interquartile range, and n represents the number of rats. P-value <0.05 is considered statistical significant.
See this image and copyright information in PMC

References

    1. Iadecola C, Davisson RL. Hypertension and Cerebrovascular Dysfunction. Cell Metab. 2008;7: 476–484. doi: 10.1016/j.cmet.2008.03.010 - DOI - PMC - PubMed
    1. Chobanian A V., Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42: 1206–1252. doi: 10.1161/01.HYP.0000107251.49515.c2 - DOI - PubMed
    1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133: e38–60. doi: 10.1161/CIR.0000000000000350 - DOI - PubMed
    1. Intengan HD, Schiffrin EL. Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension. 2001;38: 581–7. doi: 10.1161/hy09t1.096249 - DOI - PubMed
    1. Renna NF, de Las Heras N, Miatello RM. Pathophysiology of vascular remodeling in hypertension. Int J Hypertens. 2013/08/24. 2013;2013: 808353 doi: 10.1155/2013/808353 - DOI - PMC - PubMed