Department of Surgery, Texas A&M University Health Science Center College of Medicine & Baylor Scott & White Healthcare, Temple, Texas, USA.
Aging Dis. 2014 Apr 1;5(2):114-25. doi: 10.14336/AD.2014.0500114. eCollection 2014 Apr.
Vascular hyperpermeability, the excessive leakage of fluid and proteins from blood vessels to the interstitial space, commonly occurs in traumatic and ischemic injuries. This hyperpermeability causes tissue vasogenic edema, which often leads to multiple organ failure resulting in patient death. Vascular hyperpermeability occurs most readily in small blood vessels as their more delicate physical constitution makes them an easy target for barrier dysfunction. A single layer of endothelial cells, linked to one another by cell adhesion molecules, covers the interior surface of each blood vessel. The cell adhesion molecules play a key role in maintaining barrier functions like the regulation of permeability. Aging is a major risk factor for microvascular dysfunction and hyperpermeability. Apart from age-related remodeling of the vascular wall, endothelial barrier integrity and function declines with the advancement of age. Studies that address the physiological and molecular basis of vascular permeability regulation in aging are currently very limited. There have been many cellular and molecular mechanisms proposed to explain aging-related endothelial dysfunction but their true relationship to barrier dysfunction and hyperpermeability is not clearly known. Among the several mechanisms that promote vascular dysfunction and hyperpermeability, the following are considered major contributors: oxidative stress, inflammation, and the activation of apoptotic signaling pathways. In this review we highlighted (a) the physiological, cellular and molecular changes that occur in the vascular system as a product of aging; (b) the potential mechanisms by which aging leads to barrier dysfunction and vascular hyperpermeability in the peripheral and the blood-brain barrier; (c) the mechanisms by which the age-related increases in oxidative stress, inflammatory markers and apoptotic signaling etc. cause endothelial dysfunction and their relationship to hyperpermeability; and (d) the relationship between aging, vascular permeability and traumatic injuries.
血管通透性增加，即血管内的液体和蛋白质过度渗漏到组织间隙，常见于创伤和缺血性损伤。这种通透性增加导致组织血管源性水肿，常导致多器官衰竭，从而导致患者死亡。小血管最容易发生血管通透性增加，因为它们的结构更为脆弱，容易受到屏障功能障碍的影响。单层内皮细胞通过细胞黏附分子彼此连接，覆盖在每个血管的内表面。细胞黏附分子在维持屏障功能方面起着关键作用，如调节通透性。衰老也是微血管功能障碍和通透性增加的一个主要危险因素。除了血管壁的年龄相关性重塑外，内皮屏障的完整性和功能随着年龄的增长而下降。目前，关于衰老过程中血管通透性调节的生理和分子基础的研究非常有限。有许多细胞和分子机制被提出来解释与年龄相关的内皮功能障碍，但它们与屏障功能障碍和通透性增加的真正关系尚不清楚。在促进血管功能障碍和通透性增加的几种机制中，以下是主要的贡献者：氧化应激、炎症和凋亡信号通路的激活。在这篇综述中，我们重点介绍了：（a）衰老导致血管系统发生的生理、细胞和分子变化；（b）衰老导致外周和血脑屏障屏障功能障碍和血管通透性增加的潜在机制；（c）与年龄相关的氧化应激、炎症标志物和凋亡信号等增加导致内皮功能障碍及其与通透性增加的关系；（d）衰老、血管通透性和创伤性损伤之间的关系。
