The molecular basis of atherosclerosis is not fully understood and mice studies have shown that Ephrins and EPH receptors play a role in the atherosclerotic process. We set out to assess the role for monocytic EPHB2 and its Ephrin ligands in human atherosclerosis and show a role for EPHB2 in monocyte functions independently of its EphrinB ligands. Immunohistochemical staining of human aortic sections at different stages of atherosclerosis showed that EPHB2 and its ligand EphrinB are expressed in atherosclerotic plaques and that expression proportionally increases with plaque severity. Functionally, stimulation with EPHB2 did not affect endothelial barrier function, nor did stimulation with EphrinB1 or EphrinB2 affect monocyte-endothelial interactions. In contrast, reduced expression of EPHB2 in monocytes resulted in decreased monocyte adhesion to endothelial cells and a decrease in monocyte transmigration, mediated by an altered morphology and a decreased ability to phosphorylate FAK. Our results suggest that EPHB2 expression in monocytes results in monocyte accumulation by virtue of an increase of transendothelial migration, which can subsequently contribute to atherosclerotic plaque progression.
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http://dx.doi.org/10.1002/JLB.2A0320-283RR | DOI Listing |
Front Cardiovasc Med
December 2024
Seattle Children's Hospital, Seattle, WA, United States.
Introduction: The use of cardiopulmonary bypass (CPB) can induce sterile systemic inflammation that contributes to morbidity and mortality, especially in children. Patients have been found to have increased expression of cytokines and transmigration of leukocytes during and after CPB. Previous work has demonstrated that the supraphysiologic shear stresses existing during CPB are sufficient to induce proinflammatory behavior in non-adherent monocytes.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
CENECON, Faculty of Medical Sciences, Universidad de Buenos Aires, and Pontificia Universidad Catolica Argentina, Buenos Aires, Argentina.
Atherosclerosis is the underlying factor in the premature death of millions of humans annually. The cause of death is often a result of the rupture of an atherosclerotic plaque followed by the discharge of the associated molecular debris into the vessel lumen which occludes the artery leading to ischemia of downstream tissue and to morbidity or mortality of the individual. This is most serious when it occurs in the heart (heart attack) or brain (stroke).
View Article and Find Full Text PDFBiol Direct
December 2024
Department of Obstetrics and Gynecology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Background: Intrauterine adhesion (IUA) is a common cause of clinically refractory infertility, and there exists significant heterogeneity in the treatment outcomes among IUA patients with the similar severity after transcervical resection of adhesion(TCRA). The underlying mechanism of different treatment outcomes occur remains elusive, and the precise contribution of various cell subtypes in this process remains uncertain.
Results: Here, we performed single-cell transcriptome sequencing on 10 human endometrial samples to establish a single-cell atlas differences between patients who responded to estrogen therapy and those who did not.
J Tehran Heart Cent
January 2024
Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Background: Cardiovascular disease (CVD) is one of the principal causes of mortality in the world. Various factors have been identified in the pathogenesis of CVD. Leukemia inhibitory factor (LIF) as a secretory cytokine is one of these factors.
View Article and Find Full Text PDFLab Chip
December 2024
Queensland Micro- and Nanotechnology, Griffith University, Nathan, Queensland 4111, Australia.
Atherosclerosis is a chronic inflammatory vascular disorder driven by factors such as endothelial dysfunction, hypertension, hyperlipidemia, and arterial calcification, and is considered a leading global cause of death. Existing atherosclerosis models have limitations due to the absence of an appropriate hemodynamic microenvironment and interspecies differences . Here, we develop a simple but robust microfluidic intimal-lumen model of early atherosclerosis using interconnected dual channels for studying monocyte transmigration and foam cell formation at an arterial shear rate.
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