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周围的5-HT/HTR6轴负责与肥胖相关的高血压
Vadim I Chechekhin1, Anastasia M Ivanova1, Konstantin Y Kulebyakin1
1Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Lomonosov Moscow State University, Moscow 119991, Russia.
与肥胖相关的高血压涉及介酶体 stromal 细胞 (MSC). 血清激素 (5-HT) 通过HTR6受体增强诺亚上腺素诱导的MSC收缩性,这表明高血压的治疗点.
科学领域:
- 内分泌学和新陈代谢学
- 心血管生理学心血管生理学
- 细胞信号传输 细胞信号传输
背景情况:
- 高血压是肥胖的一个关键并发症.
- 脂肪介酶体 stromal 细胞 (MSCs) 通过放大 noradrenaline 诱导的血管收缩,有助于肥胖相关的高血压.
- 通过cAMP介导的信号通路与MSC驱动的血管收缩性有关.
研究的目的:
- 为了研究cAMP介导激素对脂肪性MSCs上腺素敏感性和收缩性的影响.
- 确定参与5-HT调节MSC收缩性的特定信号通路和受体.
主要方法:
- 用各种cAMP介导激素治疗脂肪性MSCs.
- 测量α1A-上腺受体诱导的Ca2+信号传递.
- 评估诺拉丁上腺素诱导的MSC收缩性.
- 使用HTR异形特异性抗剂的药理抑制.
- 使用CRISPRi技术对HTR6进行基因淘汰.
主要成果:
- 只有血清素 (5-HT) 在MSC中显著提高了α1A-上腺体受体诱导的Ca2+信号.
- 5-HT显著增强了因诺亚上腺素引起的MSC收缩性.
- 鉴定出HTR6受体异型是5-HT对MSC收缩性影响的调解者.
结论:
- 以前与中枢神经系统活动相关的HTR6受体,在调节MSC收缩性方面发挥着重要作用.
- 这一发现揭示了肥胖相关高血压的一个新机制.
- HTR6代表了预防和治疗肥胖相关高血压的潜在治疗标.
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