高脂调节TGFβ受体脂质分区,恢复胆固醇负载的血管光滑肌细胞的收缩特征
Prashanth Thevkar Nagesh1, Shruti Rawal2, Hitoo Nishi2
1Department of Medicine, Division of Cardiology, and Cardiovascular Research Center, New York University Grossman School of Medicine, New York, New York, USA; Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA.
JACC. Basic to translational science
|February 13, 2026
概括
高胆固醇导致血管光滑肌细胞 (VSMCs) 采取有害的巨类特征. 通过高密度脂蛋白 (HDL) 的胆固醇外流可以逆转这种过渡,这表明HDL是动脉样硬化的潜在治疗方法.
科学领域:
- 心血管生物学 心血管生物学
- 动脉样硬化病原体的产生
- 细胞表型可塑性 细胞表型可塑性
背景情况:
- 动脉样斑块中的巨类细胞越来越多地被认为源自血管光滑肌细胞 (VSMC).
- VSMCs的表型切换到类似巨细胞的状态与不良的动脉样硬化进展有关.
研究的目的:
- 阐明胆固醇影响动脉样硬化中的VSMC表型的机制.
- 研究高密度脂蛋白 (HDL) 介导的胆固醇外流作为恢复VSMC表型的治疗策略的潜力.
主要方法:
- 使用人类VSMC (hVSMC) 进行体外研究,以评估TGFβ信号传递,脂质中的受体定位和基因表达 (Acta2,CD68,Mir145).
- 在体内实验中,ApoA1被给予动脉样硬化小鼠,以评估斑块内VSMC的表型变化.
主要成果:
- 胆固醇的积累会通过改变TGFβ受体局部来损害hVSMC中的TGFβ信号传递,从而导致亲巨细胞表型 (CD68增加,Acta2减少).
- 高脂介导的胆固醇外流恢复了TGFβ信号传递,促进了Mir145的表达,并将VSMCs逆转为收缩型表型 (Acta2增加,CD68减少).
- 在小鼠的体内ApoA1治疗反映了这些发现,增强VSMC Acta2表达和减少动脉样硬化斑块中的CD68表达.
结论:
- 胆固醇的积累驱动VSMC通过TGFβ途径失调转变为类似巨细胞的表型.
- 通过高密度胆固醇颗粒调解的胆固醇外流可以逆转这种有害的表型开关.
- 有效流动能力的HDL代表了调节动脉样硬化中的VSMC表型的有希望的治疗途径.
相关概念视频
Cholesterol: Significance and Regulation
1.5K
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
1.5K
Functions of Smooth Muscles
3.5K
Smooth muscles are an important type of muscle tissue that plays a vital role in the involuntary movements of internal organs. For example, they help regulate the movement of food through the gut and the flow of blood through the circulatory system.
Function of visceral smooth muscles
Visceral smooth muscle is found in the walls of all hollow organs, except the heart, and is a key player in the involuntary movements that drive the functioning of these internal organs. This tissue is arranged in...
Function of visceral smooth muscles
Visceral smooth muscle is found in the walls of all hollow organs, except the heart, and is a key player in the involuntary movements that drive the functioning of these internal organs. This tissue is arranged in...
3.5K
Smooth Muscle Contraction
8.1K
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
8.1K
What are Lipids?
221.4K
Overview
221.4K
Structure and Organization of Smooth Muscles
9.1K
Smooth muscle tissue is a type of muscle tissue that can be found lining various vital organs in the human body, including the lungs, blood vessels, digestive tract, and respiratory tract. This type of tissue is responsible for regulating the movements of these organs, playing crucial roles in the functioning of various systems, including the vascular, digestive, respiratory, and urinary systems.
Structure of smooth muscle cell
Smooth muscle cells are spindle-shaped with tapering ends and a...
Structure of smooth muscle cell
Smooth muscle cells are spindle-shaped with tapering ends and a...
9.1K
Receptor-mediated Endocytosis
111.6K
Overview
111.6K


