During inflammation, the disruption of the endothelial barrier leads to increased microvascular permeability. Whether tension along cell junctions contributes to histamine-induced endothelial barrier disruption remains unknown. Rapid Ca influx induced by both histamine and thrombin was accompanied by endothelial barrier breakdown revealed as drop of transendothelial electric resistance in primary human microvascular endothelial cells. Interestingly, GLISA measurements revealed activation of RhoA but not inactivation of Rac1 at the time-point of barrier breakdown. FRET measurements showed activation of RhoA at intercellular junctions after both thrombin and histamine exposure. Breakdown coincided with increased stress fiber formation but not with translocation of vinculin, which was located along junctions in the resting state similar to postcapillary venules ex vivo. Moreover, increased tension at AJs was indicated by immunostaining with a conformation-sensitive antibody targeting the α18-subunit of α-catenin. Ca chelation by BAPTA-AM and ROCK1 inhibition by Y27632 abolished both increase of tension along AJs as well as barrier dysfunction. Moreover, BAPTA-AM decreased RhoA activation following histamine stimulation, indicating a key role of Ca signaling in barrier breakdown. Taken together, in response to histamine, Ca via RhoA/ROCK activation along endothelial adherens junctions (AJs) appears to be critical for barrier disruption and presumably correlated with enhanced tension. However, vinculin appears not to be critical in this process.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125323PMC
http://dx.doi.org/10.1038/s41598-018-31408-3DOI Listing

Publication Analysis

Top Keywords

endothelial barrier
16
barrier disruption
12
barrier breakdown
12
barrier
8
rhoa activation
8
adherens junctions
8
activation rhoa
8
tension ajs
8
appears critical
8
histamine
5

Similar Publications

The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.

View Article and Find Full Text PDF

Background: Cardiovascular risk factors (CRFs) like hypertension, high cholesterol, and diabetes mellitus are increasingly linked to cognitive decline and dementia, especially in cerebral small vessel disease (cSVD). White matter hyperintensities (WMH) are closely associated with cognitive impairment, but the mechanisms behind their development remain unclear. Blood-brain barrier (BBB) dysfunction may be a key factor, particularly in cSVD.

View Article and Find Full Text PDF

Cell-cell communications in the brain of hepatic encephalopathy: The neurovascular unit.

Life Sci

January 2025

Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea; Research Institute for Biomedical & Health Science (RIBHS), Konkuk University, Chungju, Republic of Korea. Electronic address:

Many patients with liver diseases are exposed to the risk of hepatic encephalopathy (HE). The incidence of HE in liver patients is high, showing various symptoms ranging from mild symptoms to coma. Liver transplantation is one of the ways to overcome HE.

View Article and Find Full Text PDF

Background: Myocardial ischemia-reperfusion (I/R) injury and coronary microcirculation dysfunction (CMD) are observed in patients with myocardial infarction after vascular recanalization. The antianginal drug trimetazidine has been demonstrated to exert a protective effect in myocardial ischemia-reperfusion injury.

Objectives: This study aimed to investigate the role of trimetazidine in endothelial cell dysfunction caused by myocardial I/R injury and thus improve coronary microcirculation.

View Article and Find Full Text PDF

Intrauterine adhesion (IUA) is an endometrial damage repair disorder that leads to menstrual loss, amenorrhea, and infertility in women; therefore, addressing this dilemma is a critical challenge. In this study, a multifunctional hydrogel, comprising oxidized sodium alginate (OSA), strontium carbonate (SrCO), and betamethasone 21-phosphate sodium (BSP), was formulated to facilitate angiogenesis, reduce fibrosis, and support tissue repair in the treatment of IUA. The composite hydrogels showed significant bioactivity on human endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs), promoting the injured HESCs repair, reversing the degree of fibrosis to a certain extent, and enhancing the proliferation and migration of HUVECs.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!