血小板通过分泌增长因子调节因子来调节缺血诱导的再血管化和血管生成
Henry Nording1,2, Lasse Baron1, Manuela Sauter3
1Cardioimmunology Group, Medical Clinic II, University Heart Center Lübeck, Lübeck, Germany.
Blood advances
|May 31, 2023
概括
血小板调节缺血组织中的血管生长. 补充C5a激活血小板C5a受体1 (C5aR1) 通过释放抗血管性CXCL4 (PF4) 来抑制这一过程.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
背景情况:
- 血小板在血管生成中发挥作用,新血管的形成,特别是在缺血条件下.
- 血小板调节血管生成的精确分子机制仍然不完全理解.
研究的目的:
- 为了研究补充性厌血素C5a介导的血小板C5a受体1 (C5aR1) 激活在调节缺血驱动的再血管化的作用.
- 评估患有心血管和外围动脉疾病的患者血小板C5aR1的临床相关性.
主要方法:
- 在冠状动脉和外周动脉疾病患者的血小板上评估C5aR1表达.
- 利用遗传小鼠模型 (C5aR1-/-和C5-/-小鼠) 来研究后肢缺血中的重血管化.
- 从C5a刺激的血小板中研究的血小板上浮体.
- 进行了谱系特定的C5aR1删除实验,并使用C5aR1-/-CXCL4-/-小鼠.
主要成果:
- 在后肢缺血模型中增加C5aR1表达血小板的存在.
- 在C5aR1-/-小鼠中显著改善缺血驱动的血管生成,但不是C5-/-小鼠.
- 刺激C5a的血小板释放出抗血管性CXC化学因联结物4 (CXCL4,PF4),通过膜机制抑制血管生成.
- CXCL4的分泌取决于血小板上的C5aR1结合,由谱系特异的删除和双重淘汰研究证实.
结论:
- 血小板C5aR1激活代表了一种抑制新血管化的新机制.
- 这种抑制是由血小板中C5a-C5aR1-轴依赖的抗血管性CXCL4释放的介导.
- 这些发现强调了血小板C5aR1在调节缺血期间血管形成中的特定作用.
相关概念视频
Formation of the Platelet Plug
6.7K
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
6.7K
Clot Retraction and Fibrinolysis
6.6K
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
6.6K
Structure and Function of Platelets
1.3K
The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
1.3K
Regulation of Angiogenesis and Blood Supply
2.6K
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...
2.6K
Mechanism of Angiogenesis
5.7K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.7K
Introduction to Hemostasis
8.4K
Hemostasis is a complex physiological process that prevents excessive bleeding when a blood vessel is injured. It's crucial for maintaining the integrity of the circulatory system, as it ensures that our blood remains fluid while still within the vascular network and yet clots to prevent blood loss upon vessel injury.
The three phases of hemostasis involve many clotting factors present in plasma and several substances released by platelets and injured tissue cells. It is a fast, localized,...
The three phases of hemostasis involve many clotting factors present in plasma and several substances released by platelets and injured tissue cells. It is a fast, localized,...
8.4K


