Angiotensin II inhibits the protein expression of ZO‑1 in vascular endothelial cells by downregulating VE‑cadherin

Abstract

Angiotensin II (Ang II) is reported to be involved in the development of various cardiovascular diseases by disrupting microvessel permeability, however, the underlying mechanism remains to be elucidated. The present study aimed to investigate the mechanism by which Ang II disrupts microvascular permeability. Rat endothelial cells were subjected to primary culture and identification. Cells in passages 4‑7 were then used for the following experiments. The cells were divided into control, Ang II, and Ang II + valsartan groups, and reverse transcription‑quantitative polymerase chain reaction and western blot analyses were perform to evaluate the expression of zonula occludens‑1 (ZO‑1) and vascular endothelial (VE)‑cadherin in the cells. The distribution of ZO‑1 protein was also detected using immunofluorescence assays. It was found that, compared with the control group, lower expression levels of ZO‑1 and VE‑cadherin were present in the Ang II group (P<0.01). ZO‑1 was also irregularly distributed at the periphery of the cells. In addition, the overexpression of VE‑cadherin reversed the effect of Ang II on the expression and distribution of ZO‑1 in endothelial cells. Together, these results suggested that Ang II inhibited the protein expression of ZO‑1 in vascular endothelial cells by downregulating VE‑cadherin, thus destroying the tight junctions between endothelial cells, which may also be the mechanism by which Ang II is involved in the development of cardiovascular diseases.

Soluble RAGE attenuates AngII-induced endothelial hyperpermeability by disrupting HMGB1-mediated crosstalk between AT1R and RAGE

“…VE-cadherin is a component of endothelial adherens junctions that plays a major role in the maintenance of endothelial cell–cell contact by interacting with the cytoskeleton via anchoring molecules such as β-catenin 19,42 , and its physiological regulation is compromised in Ang II-induced endothelial dysfunction 43,44 . The cytoplasmic tail of VE-cadherin contains at least five tyrosine residues (Y648, Y658, Y685, Y731, and Y733), and phosphorylation of Y731 mediated by the cytoplasmic protein tyrosine kinase Src is especially important in modulating VE-cadherin activity, since C-tail phosphorylation of VE-cadherin can lead to the dissociation of VE-cadherin from its accessory molecule β-catenin 22,45 .…”

Radiological assessment of effectiveness of soluble RAGE in attenuating Angiotensin II-induced LVH mouse model using in vivo 9.4T MRI

“…In these previous studies of CVD using animal models, differences between experimental groups were confirmed by invasive and indirect methods such as blood examination or end-point assays, like tissue staining and western blotting 17,24,37,41,43,44 . The major disadvantage of these methods is that the results from one assay are limited and discontinuous.…”

Aloe emodin relieves Ang II-induced endothelial junction dysfunction via promoting ubiquitination mediated NLRP3 inflammasome inactivation

“…In our study, we found that Ang II could significantly decrease the expression of tight junction protein ZO‐1/2, which means that Ang II could contribute to endothelial cell injury. Other studies also reported that Ang II involved in the development of various cardiovascular diseases by disrupting microvessel permeability, 22 inhibited the protein expression of ZO‑1 in vascular endothelial cells by down‐regulating vascular endothelial (VE)‑cadherin, and then destroying the tight junctions between endothelial cells 23 . Therefore, the prevention and treatment of endothelial dysfunction induced by Ang II should be taken into account.…”

“…(D) The integrity of endothelial cells was determined by detecting changes in trans endothelial electric resistance (n = 4). ** P < 0.01, angiotensin II (Ang II) vs. Control, # P < 0.05, ## P < 0.01, AE vs. Ang II.Scale bar, 20 µmdisrupting microvessel permeability,22 inhibited the protein expression of ZO-1 in vascular endothelial cells by down-regulating vascular endothelial (VE)-cadherin, and then destroying the tight junctions between endothelial cells 23. Therefore, the prevention and treatment of endothelial dysfunction induced by Ang II should be taken into…”