由自然存在的不和溶解酸诱导的血管重塑 in vivo
Kenji Yoshida1, Wataru Nishida, Ken'ichiro Hayashi
1Department of Neuroscience, Osaka University Graduate School of Medicine (D13), 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Circulation
|September 25, 2003
概括
不和 lysophosphatidic 酸 (LPA) 在体内诱导血管重塑和neointima形成,模仿人类动脉样硬化. 这项研究突出了LPA的重点.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 细胞生物学 细胞生物学
背景情况:
- Lysophosphatidic 酸 (LPA) 是参与各种细胞过程的信号脂质.
- 不和的LPAs,但不是和的,以前发现可以诱导血管光滑肌肉细胞 (VSMC) 不分化.
- 这种脱差涉及ERK和p38MAPK的激活,导致VSMC的扩散和迁移.
研究的目的:
- 为了研究不和 (18:1 LPA) 和和 (18:0 LPA) 溶解酸对血管系统的体内影响.
- 为了确定不和的LPA是否会在活体中诱导血管重塑和新密的形成.
主要方法:
- 鼠的常见动脉 (CCA) 用18:1 LPA或18:0 LPA进行治疗.
- 对治疗的CCA进行了组织学和生化分析.
- 标志物研究 ([3H]18:1 LPA) 用于评估LPA在血管壁中的融入和代谢.
主要成果:
- 18:1 LPA,但不是18:0 LPA,显著诱导了血管重塑,主要是新亲密形成.
- 在血管壁中检测到足够的非代谢的18: 1LPA,以诱导VSMC脱差.
- 18:1 LPA诱导的新亲密形成取决于ERK和p38MAPK的激活.
- 在组织学上, 18:1 用LPA治疗的CCA类似于人类动脉样硬化动脉.
结论:
- 这项研究提供了第一个证据,证明自然存在的不和LPA在诱导体内血管改造中的作用.
- 这些发现建立了一个新的动物模型来研究neointima形成.
- 不和的LPA代表了新密度形成的血管疾病的潜在治疗标.
相关概念视频
Mechanism of Angiogenesis
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...
Regulation of Angiogenesis and Blood Supply
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 hydroxylase and factor...
Vascular Spasm
The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last for...
Formation of the Platelet Plug
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...
Extrinsic and Intrinsic Pathways of Hemostasis
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
Autoregulation of Blood Flow
Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation.


