Tissue-Specific Upregulation of Angiotensin-Converting Enzyme 1 in Spontaneously Hypertensive Rats Through Histone Code Modifications
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The renin-angiotensin system has been implicated in the development of hypertension and damages several organs. The expressions of the components of a local renin-angiotensin system (RAS) in the hypertensive rats differ from those of the normotensive rats. We hypothesized that local tissue-specific upregulation of angiotensin-converting enzyme 1 (ACE1) in hypertension is caused by epigenetic changes. Adrenal gland, aorta, heart, kidney, liver, and lung tissues were excised from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Ace1 mRNA and protein expressions were measured by real-time PCR and Western blot, respectively. Promoter methylation was revealed by bisulfite sequencing. Histone modifications, such as histone 3 acetylation (H3Ac), fourth lysine trimethylation (H3K4me3), and ninth lysine dimethylation (H3K9me2), were quantified by chromatin immunoprecipitation (ChIP), followed by real-time PCR. The expressions and associations of chromatin remodeling genes were analyzed by real-time PCR and ChIP, respectively. Local tissues from SHRs showed higher expressions of Ace1 mRNA and protein than those from the WKY rats. Ace1 promoter was mostly unmethylated in all of the tissues from both strains. The Ace1 promoter regions of SHR tissues were more enriched with H3Ac and H3K4me3, except in the lungs. The adrenal glands, hearts, and kidneys of SHRs showed less enrichment with H3K9me2. Valsartan treatment in SHRs decreased local Ace1 mRNA and protein expressions, which were accompanied by higher H3K9me2, as well as less H3Ac and H3K4me3. In conclusion, ACE1 is upregulated in local tissues of SHRs via histone code modifications.
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Upregulation of angiotensin-converting enzyme 1 in spontaneously hypertensive rats compared with Wistar-Kyoto controls is associated with multiple epigenetic modifications in several tissues, including adrenal gland, aorta, heart and kidney.
“Moreover, upregulation of angiotensin-converting enzyme 1 in SHR compared with WKY controls was associated with multiple epi-genetic modifications in several tissues, such as the adrenal gland, aorta, heart and kidney199.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [199]
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Tain, Y., & Hsu, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413610 · Cited by 4 · see citing works
Epigenetics in the Developmental Origin of Cardiovascular Disorders
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Rodríguez, J. E., Andrade‐Jorge, E., Barquet-Nieto, A., Estrada-Soto, S. E., Gallardo‐Ortíz, I. A., & Villalobos‐Molina, R. (2024) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2024.130732 · Cited by 3 · see citing works
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Rewriting heart health: epigenetic drugs in cardiovascular medicine
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- Authors
- Lee, H.-A., Cho, H.-M., Lee, D.-Y., Kim, K.-C., Han, H. S., & Kim, I. K.
- Affiliations
- Kyungpook National University (KR)
- From the Department of Pharmacology (H.-A.L., H.-M.C., D.-Y.L., I.K.K.), Cardiovascular Research Institute (H.-A.L., K.-C.K., I.K.K.), Department of Physiology (H.S.H.), and Cell and Matrix Research Institute (H.-A.L., I.K.K.), Kyungpook National University School of Medicine, Daegu, Republic of Korea.
- Venue
- Hypertension
- Published
- 2012-03
- Volume
- 59
- Issue
- 3
- Pages
- 621-626
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2077359836
- Cited by
- 76
- References
- 34
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 2 · 2015: 10 · 2014: 7 · 2013: 5 · 2012: 3
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- angiotensin-converting enzyme, spontaneously hypertensive rats, local renin-angiotensin system, histone modifications, epigenetic regulation, histone H3 acetylation, H3K4me3, H3K9me2, valsartan, chromatin remodeling, tissue-specific gene expression
- MeSH terms
- Adrenal Glands, Animals, Blood Pressure, Disease Models, Animal, Hypertension, Kidney, Peptidyl-Dipeptidase A, Myocardium, Rats, Inbred SHR, Rats, Inbred WKY, Renin-Angiotensin System, RNA, Messenger, Up-Regulation, Histone Code, Rats, Real-Time Polymerase Chain Reaction
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