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Differential expression and DNA methylation of angiotensin type 1A receptors in vascular tissues during genetic hypertension development

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Abstract

Angiotensin type 1a receptor (AT1aR) is thought to play an important role in the development of hypertension. However, it is unknown how the AT1aR expression in vascular tissue is changed during the development of hypertension or if the degree of methylation in the AT1aR promoter correlates with the expression of AT1aR. To address these questions, we measured AT1aR mRNA, protein expression, and methylation status of the AT1aR promoter in the aorta and mesenteric artery of male spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats acting as controls at pre-hypertensive (4 weeks), evolving (10 weeks), and established (20 weeks) stages of hypertension. The expression of the AT1aR mRNA and protein was not different between the SHRs and WKY rats at 4 weeks. However, they were significantly greater in SHRs than in WKY rats at 20 weeks. Bisulfite sequencing revealed that the AT1aR promoter from the aorta and mesenteric artery of the SHRs was progressively hypo-methylated with age as compared with their WKY rat counterparts. These results suggest that the heightened AT1aR expression in SHRs is related to the AT1aR promoter hypo-methylation, which might be a consequence of the increased blood pressure and may be important in the maintenance of high blood pressure.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81200193 and No. 81273507).

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None declared.

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    Authors and Affiliations

    1. Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, 30 Gaotanyan, Shapingba District, Chongqing, 400038, China

      Fang Pei & Xiaohui Li

    2. Department of Cardiology, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Rd, Yuzhong District, Chongqing, 400042, China

      Fang Pei, Xinquan Wang, Rongchuan Yue, Caiyu Chen & Chunyu Zeng

    3. Department of Cardiology, Chongqing Corps Hospital of Chinese People’s Armed Police Force, No. 90, Marbles Shi Weiguo Road, Nanan District, Chongqing, 400061, China

      Fang Pei, Ji Huang & Jie Huang

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    1. Fang Pei
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    Correspondence to Xiaohui Li or Chunyu Zeng.

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    Fang Pei and Xinquan Wang have contributed equally to this work.

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    Pei, F., Wang, X., Yue, R. et al. Differential expression and DNA methylation of angiotensin type 1A receptors in vascular tissues during genetic hypertension development. Mol Cell Biochem 402, 1–8 (2015). https://doi.org/10.1007/s11010-014-2295-9

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    • DOI: https://doi.org/10.1007/s11010-014-2295-9

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