Recent Advances in Hypertension: Epigenetic Mechanism Involved in Development of Salt-Sensitive Hypertension
| Autor: | Toshiro Fujita |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Hypertension. |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.122.20588 |
| Popis: | This review highlights recent insights into the epigenetic mechanism of salt-sensitive hypertension from the fetus to the elderly population, mainly focusing on the DNA methylation and histone modification-mediated regulation of hypertension-associated genes. Maternal malnutrition during pregnancy induces upregulation of angiotensin receptor 1a ( AT1a ) by aberrant DNA methylation, and increased AT1A activity in the hypothalamus develops prenatally programmed salt-sensitive hypertension through renal sympathetic overactivity. In addition, maternal lipopolysaccharide exposure during pregnancy induces upregulation of the Rac1 gene through histone modification by H3K9me2 across generations, resulting in salt-induced activation of the Rac1-MR (mineralocorticoid receptor) pathway in the kidney and the development of salt-sensitive hypertension in F4 and F5 offspring. In mice, aberrant DNA methylation of the Klotho gene, which regulates aging-associated hypertension, decreases the circulating soluble Klotho levels, leading to activation of the vascular Wnt5a-RhoA pathway and vasoconstriction and development of salt-sensitive hypertension because of decreased renal blood flow. A detailed understanding of the environmentally-induced epigenetic modulations related to salt-induced hypertension could be promising for developing preventive and therapeutic approaches to hypertension. |
| Databáze: | OpenAIRE |
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