Hypoxia and reoxygenation stimulate biphasic changes in endothelial monolayer permeability

Abstract

Incubation of bovine pulmonary microvascular endothelial (BPMVE) cells in low O2 content (95% N2-5% CO2) for 4 h increased monolayer permeability to dextran almost twofold and also increased the incidence of intercellular gaps and intracellular actin stress fibers. Hypoxic incubation decreased the extracellular matrix contents of fibronectin and vitronectin, proteins that serve as anchorage points for the endothelial cells. This state was reversed after 24 h of hypoxic incubation, and the BPMVE monolayer permeability to dextran was less than that of normoxic controls. The monolayer had fewer intercellular gaps and stress fibers, and the extracellular matrix contained increased amounts of fibronectin, vitronectin, and type I collagen. These alterations stimulated by 24 h of hypoxic incubation were resolved within 4 h of reoxygenation in room air supplemented with 5% CO2. These studies indicate that incubation of endothelial monolayers in hypoxic conditions first increases and then decreases monolayer permeability, through increased and decreased formation of intercellular gaps.

Pulmonary Microvascular Endothelial Cells Form a Tighter Monolayer when Grown in Chronic Hypoxia

“…Many published papers report that acute hypoxia increases endothelial monolayer permeability (11,12,19) and may do so in part through activation of Rho/Rho kinase (11,13). Our preliminary data demonstrate that PMVEC grown to confluence in hypoxia have decreased monolayer permeability, however.…”

“…In 1995, Catherine Partridge demonstrated that the permeability of a confluent monolayer of (bovine pulmonary artery) endothelial cells increased within the first 4 to 6 hours after exposure to hypoxia (3% oxygen), although by 24 hours, the permeability of the monolayer had actually decreased relative to baseline (12). More recent studies have also demonstrated an increase in monolayer permeability in cells exposed to hypoxia.…”

“…In in vitro experiments, hypoxia can disrupt monolayer integrity and increase endothelial permeability (10)(11)(12). Activation of the RhoA/Rho kinase signaling pathway coupled with inhibition of Rac1 is thought to account for at least part of this increased permeability (11,13).…”

Matrix Metalloproteinase Inhibition Decreases Ischemia-Reperfusion Injury After Lung Transplantation

“…The PMNendothelial cells interaction (12) and the release of proinflammatory cytokines such as tumor necrosis alpha (TNF-a) and interleukin-1 (IL-1) amplify inflammatory cell recruitment, extravasation and favor vascular permeability alteration and tissue edema (13)(14)(15). While neutrophil transendothelial migration and its pathological consequences are well documented (16)(17)(18), significantly less is known of the mechanisms by which inflammatory cells cross or degrade (19) the basement membrane and infiltrate the surrounding extracellular matrix (ECM) (20).…”

Regulation of vimentin intermediate filaments in endothelial cells by hypoxia

“…Signaling pathways that are activated by hypoxia such as p38 mitogen-activate protein (MAP) kinase and Rho kinase pathways alter the actin cytoskeleton and contractile proteins leading to changes in biomechanical forces in these cells (3). These forces likely play an important role in endothelial cell migration and interaction with leukocytes as well as in regulation of endothelial barrier permeability which is altered in hypoxia (10,14,19). Intermediate filaments constitute one of the three major components of the cytoskeleton which also include actin microfilaments and tubulin microtubules.…”