Abstract The vascular endothelium is an interface between the blood stream and the vessel wall. Changes in this single cell layer of the artery wall are believed of primary importance in the pathogenesis of vascular disease/atherosclerosis. The endothelium responds to humoral, neural and especially hemodynamic stimuli and regulates platelet function, inflammatory responses, vascular smooth muscle cell growth and migration, in addition to modulating vascular tone by synthesizing and releasing vasoactive substances. Compromised endothelial function contributes to the pathogenesis of cardiovascular disease; endothelial ‘dysfunction’ is associated with risk factors, correlates with disease progression, and predicts cardiovascular events. Therapies for atherosclerosis have been developed, therefore, that are directed towards improving endothelial function.
By its strategic position at the interface between blood and tissues, endothelial cells control blood fluidity and continued tissue perfusion while simultaneously they direct inflammatory cells to areas in need of defense or repair. The endothelial response depends on specific tissue needs and adapts to local stresses. Endothelial cells counteract coagulation by providing tissue factor and thrombin inhibitors and receptors for protein C activation. The receptor PAR-1 is differentially activated by thrombin and the activated protein C/EPCR complex, resulting in antithrombotic and anti-inflammatory effects. Thrombin and vasoactive agents release von Willebrand factor as ultra-large platelet-binding multimers, which are cleaved by ADAMTS13. Platelets can also facilitate leukocyte-endothelium interaction. Platelet activation is prevented by nitric oxide, prostacyclin, and exonucleotidases. Thrombin-cleaved ADAMTS18 induces disintegration of platelet aggregates while tissue-type plasminogen activator initiates fibrinolysis. Fibrin and products of platelets and inflammatory cells modulate the angiogenic response of endothelial cells and contribute to tissue repair.
Background: To assess corneal endothelial cell changes after intravitreal dexamethasone (DEX) implant (Ozurdex (R)) injection in patients with macular edema secondary to retinal vein occlusion (RVO). Methods: Twenty-two eyes of 22 patients were assessed prospectively after intravitreal 0.7 mg DEX implant injection. Twenty-two eyes of 22 healthy volunteers served as control group. Corneal endothelial cell parameters including endothelial cell density (ECD), coefficient of variation of cell size (CV), percentage of hexagonality (Hex) and central corneal thickness (CCT) were analyzed before and 1 and 3 months after injection by specular microscopy. The results of the study were compared statistically. Results: There were 17 (77.3%) patients with branch RVO and 5 (22.7%) patients with central RVO. Mean intraocular pressure (IOP) was 14.73 mmHg before injection, 17.05 mmHg at 1 month and 17.15 mmHg at 3 months after injection. Mean IOP at 1 and 3 months were significantly higher than pre-injection value (p = 0.002 and p = 0.003, respectively). There was a statistically significant reduction in mean ECD at 3 months after injection compared to pre-injection and 1 month (p = 0.013, p = 0.009, respectively) in the injected eyes. Mean ECD showed no significant difference in the uninjected fellow eyes during the follow up (p>0.05). Mean CV and Hex did not reveal a statistically significant difference in injected and uninjected fellow eyes (p > 0.05). No significant change was observed in mean CCT values during the follow up (p = 0.8). Conclusion: Intravitreal dexamethasone implant may cause a transient reduction in corneal endothelial cell density in short term without changing cell morphology.
Abstract Late-onset dementia is a major health concern in the ageing population. Alzheimer's disease (AD) accounts for the largest proportion (65–70%) of dementia cases in the older population. Despite considerable research effort, the pathogenesis of late-onset AD remains unclear. Substantial evidence suggests that the neurodegenerative process is initiated by chronic cerebral hypoperfusion (CCH) caused by ageing and cardiovascular conditions. CCH causes reduced oxygen, glucose and other nutrient supply to the brain, with direct damage not only to the parenchymal cells, but also to the blood–brain barrier (BBB), a key mediator of cerebral homeostasis. BBB dysfunction mediates the indirect neurotoxic effects of CCH by promoting oxidative stress, inflammation, paracellular permeability, and dysregulation of nitric oxide, a key regulator of regional blood flow. As such, BBB dysfunction mediates a vicious circle in which cerebral perfusion is reduced further and the neurodegenerative process is accelerated. Endothelial interaction with pericytes and astrocytes could also play a role in the process. Reciprocal interactions between vascular dysfunction and neurodegeneration could further contribute to the development of the disease. A comprehensive overview of the complex scenario of interacting endothelium-mediated processes is currently lacking, and could prospectively contribute to the identification of adequate therapeutic interventions. This study reviews the current literature of in vitro and ex vivo studies on endothelium-mediated mechanisms underlying vascular dysfunction in AD pathogenesis, with the aim of presenting a comprehensive overview of the complex network of causative relationships. Particular emphasis is given to vicious circles which can accelerate the process of neurovascular degeneration.