内甲素-1降低核因子红色素2相关因子-2的调节,并有助于肥胖的周围血管脂肪组织功能障碍
Anna Flavia R Lima1, Daniel Rodrigues1, Mirele R Machado1
1Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Clinical science (London, England : 1979)
|August 13, 2024
概括
肥胖会通过增加内甲素-1 (ET-1) 来损害周血管脂肪组织 (PVAT) 功能,从而降低抗氧化防御和血管保护. 用Bosentan阻断ET-1受体恢复了PVAT功能,突出了与肥胖相关的血管问题的治疗目标.
科学领域:
- 心血管科学 心血管科学
- 代谢性疾病研究研究
- 脂肪组织生物学 脂肪组织生物学
背景情况:
- 周血管脂肪组织 (PVAT) 通常通过调节光滑肌肉收缩来提供血管保护.
- 肥胖会破坏PVAT功能,导致血管收缩剂的释放,如内甲素-1 (ET-1).
- 在肥胖中,ET-1 促成氧化应激和血管功能受损.
研究的目的:
- 研究ET-1在肥胖引起的PVAT功能障碍中的作用.
- 为了确定肥胖是否影响PVAT中的核因素红色素2相关因子-2 (Nrf2) 途径.
- 评估阻断ET-1受体在恢复PVAT功能的治疗潜力.
主要方法:
- 雄性C57BL/6小鼠被食标准或高脂肪饮食16周.
- 小鼠接受了盐水或博森坦 (ETA/ETB受体对抗剂) 治疗.
- 评估了血管功能,PVAT ET-1产生,基因表达 (ECE1,ETA,Nrf2目标),ROS水平和Nrf2活性.
主要成果:
- 肥胖小鼠的PVATET-1产量增加,ECE1/ETA表达,ROS,Nrf2活性降低和抗氧化基因表达.
- 肥胖小鼠失去了PVAT的抗收缩作用,与增加的p-GSK3β (Tyr216) 和KEAP1.1相关.
- 博森坦治疗在肥胖小鼠中逆转了所有观察到的有害影响;ET-1在棕色脂肪细胞中模仿了这些影响.
结论:
- 肥胖诱导的ET-1是PVAT功能障碍,氧化应激和血管保护作用受损的关键驱动因素.
- 减少PVAT中的Nrf2活性和抗氧化能力有助于肥胖患者的血管功能障碍.
- 对ET-1信号的药理抑制有效地恢复了PVAT的保护功能,提供了一个潜在的治疗策略.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Hormonal Regulation of Blood Pressure
2.5K
Endocrinal or hormonal intervention in the cardiovascular system is predominantly exerted by the catecholamines - epinephrine and norepinephrine, as well as a slew of hormones that interact with renal function to modulate blood volume.
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
2.5K


