Role of Vascular Endothelial-Cadherin and p120-Catenin in the Formation of Experimental Intracranial Aneurysm in Animals.

BACKGROUND: Dysfunction of endothelial cells (ECs) constitutes a critical factor in the formation of intracranial aneurysms (IAs). However, little is known about the response of ECs to hemodynamic insults and its contribution to IA formation. METHODS: IAs models were constructed in both adult female New Zealand white rabbits and male Sprague-Dawley rats. Morphologic changes of vessel wall were detected by hematoxylin and eosin staining. Molecular and cellular changes, including p120-catenin (p120ctn) and vascular endothelial-cadherin, in the median sagittal section of the artery bifurcation were analyzed by fluorescent staining. RESULTS: Destructive aneurysmal remodeling and the formation of morphologic IAs were observed at the basilar termini of experimental rabbits and the anterior cerebral artery-olfactory artery bifurcation of rats. The expression of p120ctn colocalized with vascular endothelial-cadherin in ECs decreased. Moreover, the expression of p120ctn colocalized with nucleus of ECs increased. These events suggested that p120ctn was transported from the membrane to the nucleus of ECs. CONCLUSIONS: The potential mechanism, that IAs are always localizing in the bifurcation apices, may be that the endothelium injury of vessel wall can be induced by different hemodynamic conditions. Hemodynamic changes in artery bifurcation may initiate the formation of IAs.

Knockdown of P120 catenin aggravates endothelial injury under an impinging flow by inducing breakdown of adherens junctions.

At present, the mechanisms underlying intracranial aneurysm (IA) development remain unclear; however, hemodynamics is considered a crucial factor in the induction of IA. To elucidate the association between hemodynamics and endothelial cell (EC) functions, a modified T chamber system was designed to simulate the adjustable hemodynamic conditions of an artery bifurcation. Normal human umbilical vein ECs (HUVECs) and HUVECs with P120 catenin (P120ctn) knockdown were cultured on coverslips and placed in the chamber. A flow rate of 250 or 500 ml/min impinged on the cell layer. Subsequently, the expression levels of P120ctn and other proteins, and EC morphological alterations, were examined. In normal HUVECs, after 3 h under a flow rate of 500 ml/min, the expression levels of P120ctn, vascular endothelial (VE)­Cadherin, Kaiso and α­catenin were decreased, whereas matrix metalloproteinase­2 (MMP­2) was increased. In HUVECs with P120ctn knockdown, the period during which ECs adhered to the coverslip was reduced to 1 h under a flow rate of 500 ml/min. In addition, the expression levels of VE­Cadherin, Kaiso and α­catenin in ECs were decreased, whereas those of MMP­2 were increased after 1 h; more prominent alterations were detected under a 500 ml/min flow rate compared with a 250 ml/min flow rate. Adherens junctions (AJs) are critical to the maintenance of normal morphology and EC functioning in the vascular wall, and P120ctn is an important regulator of AJs. Loss of P120ctn may be induced by hemodynamic alterations. In response to changes in hemodynamic conditions, a loss of P120ctn may aggravate AJs between ECs, thus inducing inflammation in the vascular wall. Clinically, hemodynamic alterations may result in a loss of P120ctn and endothelial injury; therefore, P120ctn may have a critical role in inducing intracranial aneurysms.

Effects of preadmission beta-blockers on neurogenic stunned myocardium after aneurysmal subarachnoid hemorrhage: A meta- analysis.

OBJECTIVE: Spontaneous subarachnoid hemorrhage is mostly caused by the rupture of an aneurysm. Neurogenic stunned myocardium (NSM) is one of the most frequent complications caused by aneurysmal subarachnoid hemorrhage (aSAH). The possible pathogenesis of NSM may be that the catecholamine peak resulting from aSAH leads to subendocardial ischemia or coronary artery spasm. We designed this meta-analysis to find out whether beta-blockers (BB) can significantly reduce the incidence of NSM and improve the outcomes of aSAH. PATIENTS AND METHODS: We systematically searched PubMed, Embase, Cochrane library, Elsevier and Medline from inception to Feb 2016. All studies related to the preadmission beta-blocker with aSAH were included. RESULTS: Three retrospective studies and 691 patients were included. The incidence of mortality [OR=0.68, 95%CI (0.08-3.50), P=0.57], cardiac dysfunction [OR = 0.55, 95% CI (0.05-6.49), P=0.63], cerebral vasospasm (OR=0.52 95% CI(0.18-2.56), P=0.50] had no statistical difference between the preadmission BB group and no BB group. CONCLUSION: The preadmission beta-blocker cannot decrease the incidence of mortality, cardiac dysfunction, cerebral vasospasm in patients with aSAH. A further research of the usefulness of preadmission beta-blocker in patients with aSAH will be needed.