IMR Press / FBL / Volume 27 / Issue 6 / DOI: 10.31083/j.fbl2706191
Open Access Original Research
Hypertension-Associated Genes in the Mesenteric Artery of Three Spontaneously Hypertensive Rat Substrains Identified Using a DNA Array Method
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1 Tougenkai Dermatology, Osaka-city, 540-8511 Osaka, Japan
2 Department of Dermatology, Self-Defense Forces Central Hospital, Setagaya-ward, 154-8532 Tokyo, Japan
3 Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ward, 113-0033 Tokyo, Japan
4 Kosho Clinic, Nishinomiya-city, 662-0051 Hyogo, Japan
5 Department of Pharmacology, Kindai University School of Medicine, Osaka-Sayama-city, 589-8511 Osaka, Japan
6 Department of Social and Environmental Medicine, Faculty of Medicine, Saga University, Saga-city, 849-8501 Saga, Japan
*Correspondence: hhigasino3@osaka.zaq.jp (Hideaki Higashino)
Academic Editor: José Luis Pérez-Castrillón
Front. Biosci. (Landmark Ed) 2022, 27(6), 191; https://doi.org/10.31083/j.fbl2706191
Submitted: 21 April 2022 | Revised: 16 May 2022 | Accepted: 26 May 2022 | Published: 15 June 2022
(This article belongs to the Special Issue Genetics and Chronic Disease)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Although the mesenteric artery plays a key role in regulating peripheral blood pressure, the molecular mechanisms that underlie the development of essential hypertension are not yet fully understood. Materials and Methods: We explored candidate genes for hypertension using three related strains of spontaneously hypertensive rats (SHRs) that mimic human essential hypertension. In this study we used DNA microarrays, a powerful tool for studying genetic diseases, to compare gene expression in the mesenteric artery of three SHR substrains: SHR, stroke-prone SHR (SHRSP), and malignant SHRSP (M-SHRSP). Results: Compared to normotensive 6-week old Wistar Kyoto rats (WKY), higher blood pressure correlated with overexpression of 31 genes and with down regulation of 24 genes. Adam23, which negatively regulates potassium current, and the potassium channel genes, Kcnc2 and Kcnq5, were associated with the onset of hypertension. In addition, Spock2 and Agtrap were identified as strengtheners of hypertension by analyzing up and down regulated genes at 9-weeks of age. Conclusions: Adam23, Kcnc2 and Kcnq5 appear to be factors for the onset of hypertension, while Spock2 and Agtrap are as factors that strengthen hypertension. These findings contribute to our understanding of the pathophysiology of hypertension and to the development of treatment for this condition.

Keywords
hypertension
stroke
DNA microarray
gene expression analyses
genomics
mesenteric artery
spontaneously hypertensive rat (SHR)
stroke-prone spontaneously hypertensive rat (SHRSP)
malignant stroke-prone spontaneously hypertensive rat (M-SHRSP)
potassium voltage-gated chanell subfamilies
Figures
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