Details

Autor(en) / Beteiligte

• Kovács, Kinga Bernadett
• Szalai, Laura
• Szabó, Pál
• Gém, Janka Borbála
• Barsi, Szilvia
• Szalai, Bence
• Perey-Simon, Bernadett
• Turu, Gábor
• Tóth, András Dávid
• Várnai, Péter
• Hunyady, László
• Balla, András

Titel

An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression

Ist Teil von

• International journal of molecular sciences, 2023-02, Vol.24 (4), p.3968

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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 is significantly upregulated in response to AngII stimulus. The 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 upregulation is type 1 angiotensin II receptor- and G activity-dependent. Furthermore, p38 MAPK has a crucial role in the upregulation of . 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 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.