Angiotensin II increases the permeability and PV-1 expression of endothelial cells

Abstract

Angiotensin II (ANG II), the major effector molecule of the renin-angiotensin system (RAS), is a powerful vasoactive mediator associated with hypertension and renal failure. In this study the permeability changes and its morphological attributes in endothelial cells of human umbilical vein (HUVECs) were studied considering the potential regulatory role of ANG II. The effects of ANG II were compared with those of vascular endothelial growth factor (VEGF). Permeability was determined by 40 kDa FITC-Dextran and electrical impedance measurements. Plasmalemmal vesicle-1 (PV-1) mRNA levels were measured by PCR. Endothelial cell surface was studied by atomic force microscopy (AFM), and caveolae were visualized by transmission electron microscopy (TEM) in HUVEC monolayers. ANG II (10−7 M), similarly to VEGF (100 ng/ml), increased the endothelial permeability parallel with an increase in the number of cell surface openings and caveolae. AT1 and VEGF-R2 receptor blockers (candesartan and ZM-323881, respectively) blunted these effects. ANG II and VEGF increased the expression of PV-1, which could be blocked by candesartan or ZM-323881 pretreatments and by the p38 mitogem-activated protein (MAP) kinase inhibitor SB-203580. Additionally, SB-203580 blocked the increase in endothelial permeability and the number of surface openings and caveolae. In conclusion, we have demonstrated that ANG II plays a role in regulation of permeability and formation of cell surface openings through AT1 receptor and PV-1 protein synthesis in a p38 MAP kinase-dependent manner in endothelial cells. The surface openings that increase in parallel with permeability may represent transcellular channels, caveolae, or both. These morphological and permeability changes may be involved in (patho-) physiological effects of ANG II.

Systemic angiotensin II and exercise-induced neurogenesis in adult rat hippocampus

“…As mentioned before, Ang II increases vascular permeability (Bodor et al, 2011;Fleegal-DeMotta et al, 2009), raising the possibility that systemic Ang II could enter the hippocampus. Indeed, pharmacological evidence suggests a role for Ang II in the hippocampal functions of memory and cognition (Gard, 2002;Akhavan et al, 2008;Bild et al, 2013), although the expression of AT1R in the adult rat hippocampus is relatively low, with the exception of the subiculum (Tsutsumi and Saavedra, 1991).…”

“…Although VEGF in blood cannot pass through the blood-brain barrier (BBB), it can open endothelial fenestrae (Dobrogowska et al, 1998) and/or promote angiogenesis (Amaral et al, 2001). In addition to VEGF, Ang II also increases vascular permeability by opening endothelial fenestrae (Bodor et al, 2011;Fleegal-DeMotta et al, 2009). The resultant increased vascular permeability may allow systemic VEGF to enter the hippocampal parenchyma and act on neural stem cells directly.…”

Activation of endothelial NAD(P)H oxidase accelerates early glomerular injury in diabetic mice

“…21 PV-1 is not expressed in the mature glomerular endothelial cells but is re-expressed in Thy1.1 nephritis, presumably reflecting a process of restorative remodeling of the glomerular capillary tuft after injury. 21 Although the exact functions of PV-1 are not clear, evidence suggests that it is involved in the control of capillary permeability by acting on the capillary wall 35 and may have a role in the development of diabetic nephropathy and albuminuria. In the present study, we detected significantly higher levels of PV-1 on the endothelial cells of NOX2TG-Akita mice compared with those of Akita, NOXT2G, and WT mice.…”

Bacteria and endothelial cells: a toxic relationship

“…For instance, recently it has become increasingly clear that statins and angiotensin receptor blockers exert protective effects on the vasculature during infection [38–40]. Though several studies have proposed mechanisms of how these drugs protect ECs by strengthening them in a general manner [41–43], they may in some cases also act by protecting ECs from the actions of toxins, as has been shown for Ply in a mouse model of sickle cell disease [44]. Additional research into the effects of these and other drugs on the endothelium, bacteria, and bacterial toxins could be important as they could uncover novel strategies to protect the endothelium from infectious insults.…”