Details

Autor(en) / Beteiligte

• Chechekhin, Vadim I
• Ivanova, Anastasia M
• Kulebyakin, Konstantin Y
• Antropova, Yulia G
• Karagyaur, Maxim N
• Skryabina, Maria N
• Chechekhina, Elizaveta S
• Basalova, Natalia A
• Grigorieva, Olga A
• Sysoeva, Veronika Yu
• Kalinina, Natalia I
• Tkachuk, Vsevolod A
• Tyurin-Kuzmin, Pyotr A

Titel

Peripheral 5-HT/HTR6 axis is responsible for obesity-associated hypertension

Ist Teil von

• Biochimica et biophysica acta. Molecular cell research, 2024-02, Vol.1871 (2), p.119651-119651, Article 119651

Ort / Verlag

Netherlands

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Hypertension is one of the major life-threatening complications of obesity. Recently adipose multipotent mesenchymal stromal cells (MSCs) were implicated to the pathogenesis of obesity-associated hypertension. These cells amplify noradrenaline-induced vascular cell contraction via cAMP-mediated signaling pathway. In this study we tested the ability of several cAMP-mediated hormones to affect the adrenergic sensitivity of MSCs and their associated contractility. Despite that adipose MSCs express a plethora of receptors capable of cAMP signaling activation, only 5-HT was able to elevate α1A-adrenoceptor-induced Ca signaling in MSCs. Furthermore, 5-HT markedly enhanced noradrenaline-induced MSCs contractility. Using HTR isoform-specific antagonists followed by CRISPRi-mediated knockdown, we identified that the observed 5-HT effect on MSCs was mediated by the HTR6 isoform. This receptor was previously associated exclusively with 5-HT central nervous system activity. Discovered effect of HTR6 on MSCs contractility points to it as a potential therapeutic target for the prevention and treatment of obesity-associated hypertension.