An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression
Angiotensin II (AngII) is a vasoactive peptide hormone, which, under pathological conditions, contributes to the development of cardiovascular diseases. Oxysterols, including 25-hydroxycholesterol (25-HC), the product of cholesterol-25-hydroxylase (CH25H), also have detrimental effects on vascular h...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3968 |
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| author | Kinga Bernadett Kovács Laura Szalai Pál Szabó Janka Borbála Gém Szilvia Barsi Bence Szalai Bernadett Perey-Simon Gábor Turu András Dávid Tóth Péter Várnai László Hunyady András Balla |
| author_facet | Kinga Bernadett Kovács Laura Szalai Pál Szabó Janka Borbála Gém Szilvia Barsi Bence Szalai Bernadett Perey-Simon Gábor Turu András Dávid Tóth Péter Várnai László Hunyady András Balla |
| author_sort | Kinga Bernadett Kovács |
| collection | DOAJ |
| description | Angiotensin II (AngII) is a vasoactive peptide hormone, which, under pathological conditions, contributes to the development of cardiovascular diseases. Oxysterols, including 25-hydroxycholesterol (25-HC), the product of cholesterol-25-hydroxylase (CH25H), also have detrimental effects on vascular health by affecting vascular smooth muscle cells (VSMCs). We investigated AngII-induced gene expression changes in VSMCs to explore whether AngII stimulus and 25-HC production have a connection in the vasculature. RNA-sequencing revealed that <i>Ch25h</i> is significantly upregulated in response to AngII stimulus. The <i>Ch25h</i> mRNA levels were elevated robustly (~50-fold) 1 h after AngII (100 nM) stimulation compared to baseline levels. Using inhibitors, we specified that the AngII-induced <i>Ch25h</i> upregulation is type 1 angiotensin II receptor- and G<sub>q/11</sub> activity-dependent. Furthermore, p38 MAPK has a crucial role in the upregulation of <i>Ch25h</i>. We performed LC-MS/MS to identify 25-HC in the supernatant of AngII-stimulated VSMCs. In the supernatants, 25-HC concentration peaked 4 h after AngII stimulation. Our findings provide insight into the pathways mediating AngII-induced <i>Ch25h</i> upregulation. Our study elucidates a connection between AngII stimulus and 25-HC production in primary rat VSMCs. These results potentially lead to the identification and understanding of new mechanisms in the pathogenesis of vascular impairments. |
| first_indexed | 2024-03-11T08:41:44Z |
| format | Article |
| id | doaj.art-4c2050e495a449d087f217f103c1d84f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:41:44Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4c2050e495a449d087f217f103c1d84f2023-11-16T21:07:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244396810.3390/ijms24043968An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene ExpressionKinga Bernadett Kovács0Laura Szalai1Pál Szabó2Janka Borbála Gém3Szilvia Barsi4Bence Szalai5Bernadett Perey-Simon6Gábor Turu7András Dávid Tóth8Péter Várnai9László Hunyady10András Balla11Department of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryResearch Center for Natural Sciences, Center for Structural Study, MS Metabolomics Laboratory, 1117 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryAngiotensin II (AngII) is a vasoactive peptide hormone, which, under pathological conditions, contributes to the development of cardiovascular diseases. Oxysterols, including 25-hydroxycholesterol (25-HC), the product of cholesterol-25-hydroxylase (CH25H), also have detrimental effects on vascular health by affecting vascular smooth muscle cells (VSMCs). We investigated AngII-induced gene expression changes in VSMCs to explore whether AngII stimulus and 25-HC production have a connection in the vasculature. RNA-sequencing revealed that <i>Ch25h</i> is significantly upregulated in response to AngII stimulus. The <i>Ch25h</i> mRNA levels were elevated robustly (~50-fold) 1 h after AngII (100 nM) stimulation compared to baseline levels. Using inhibitors, we specified that the AngII-induced <i>Ch25h</i> upregulation is type 1 angiotensin II receptor- and G<sub>q/11</sub> activity-dependent. Furthermore, p38 MAPK has a crucial role in the upregulation of <i>Ch25h</i>. We performed LC-MS/MS to identify 25-HC in the supernatant of AngII-stimulated VSMCs. In the supernatants, 25-HC concentration peaked 4 h after AngII stimulation. Our findings provide insight into the pathways mediating AngII-induced <i>Ch25h</i> upregulation. Our study elucidates a connection between AngII stimulus and 25-HC production in primary rat VSMCs. These results potentially lead to the identification and understanding of new mechanisms in the pathogenesis of vascular impairments.https://www.mdpi.com/1422-0067/24/4/3968angiotensin IIatherosclerosischolesterol-25-hydroxylase25-hydroxycholesterolvascular smooth muscle cell |
| spellingShingle | Kinga Bernadett Kovács Laura Szalai Pál Szabó Janka Borbála Gém Szilvia Barsi Bence Szalai Bernadett Perey-Simon Gábor Turu András Dávid Tóth Péter Várnai László Hunyady András Balla An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression International Journal of Molecular Sciences angiotensin II atherosclerosis cholesterol-25-hydroxylase 25-hydroxycholesterol vascular smooth muscle cell |
| title | An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression |
| title_full | An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression |
| title_fullStr | An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression |
| title_full_unstemmed | An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression |
| title_short | An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression |
| title_sort | unexpected enzyme in vascular smooth muscle cells angiotensin ii upregulates cholesterol 25 hydroxylase gene expression |
| topic | angiotensin II atherosclerosis cholesterol-25-hydroxylase 25-hydroxycholesterol vascular smooth muscle cell |
| url | https://www.mdpi.com/1422-0067/24/4/3968 |
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