Premium
Rho‐dependent upregulation of endothelial contractility and adhesion disassembly contributes to the enhanced permeability responses to inflammation in diabetic venules
Author(s) -
Yuan Dong,
He Pingnian
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.855.8
Subject(s) - contractility , streptozotocin , microvessel , downregulation and upregulation , medicine , platelet activating factor , endocrinology , chemistry , inflammation , vascular permeability , diabetes mellitus , immunohistochemistry , biochemistry , gene
Diabetes mellitus (DM) often results in microvascular complications. Our study demonstrated that DM vessels have moderately increased basal permeability, but manifested augmented responses to platelet activating factor, PAF. The objective of this study is to investigate the mechanisms involved in the increased susceptibility of DM venules to inflammation. Experiments were conducted in individually perfused mesenteric venules of normal and streptozotocin‐induced DM rats. Microvessel permeability was measured by hydraulic conductivity Lp and the changes of VE‐cadherin and F‐actin were examined using confocal imaging with immunostaining. In normal venules, pre‐perfusing Rho kinase inhibitor Y‐27632 (30 μM) did not affect basal Lp but reduced PAF‐induced peak Lp from 10 ± 1.7 to 2 ± 0.4 times the control value. In DM venules, Y‐27632 restored the increased basal Lp to a normal range and markedly reduced PAF‐induced Lp peak from 115 ± 20.0 to 11 ± 2.1 × 10 −7 cm.s −1 .cmH 2 O − 1 . In Y‐27632 perfused DM vessels, PAF‐induced apparent separation of VE‐cadherin between endothelial cells was restored to the pattern of frequent breaks observed in normal vessels exposed to PAF, and phalloidin staining showed reduced endothelial stress fiber assembly at PAF induced Lp peak. Our results indicated that Rho kinase‐mediated upregulation of endothelial contractility and adhesion disassembly contributes to the augmented PAF response in DM microvessels. Supported by HL56237 and HL084338.