Microfluidic model of monocyte extravasation reveals the role of hemodynamics and subendothelial matrix mechanics in regulating endothelial integrity

Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone, cell adhesion and the homoeostasis of clotting and fibrinolysis. The degeneration of endothelial integrity promotes adverse events leading to atherogenesis. Circulating levels of endogenous hormones decline during ageing and this may contribute to the occurrence of major adverse cardiovascular events, independently of gender differences. During the last decade more attention has been drawn to the importance of testosterone, oestradiol and adrenal androgens in the pathophysiology, prevention and treatment of male ageing-associated diseases. A considerable body of literature is available indicating that steroid hormones, particularly the sex steroids, are known to modulate endothelial function in all vascular beds and their deficiency may promote endothelial dysfunction. Testosterone decrease and increased mineralocorticoid activity in the ageing male are frequent and may yield endothelial dysfunction and increased cardiovascular burden; we recommend careful hormonal investigations in men who present comorbidities such as diabetes, hypertension and dyslipidaemia.

Download Full-text

Pulmonary Biomarkers of Bronchopulmonary Dysplasia

Biomarker Insights ◽

10.4137/bmi.s834 ◽

2008 ◽

Vol 3 ◽

pp. BMI.S834 ◽

Cited By ~ 32

Author(s):

Alecia Thompson ◽

Vineet Bhandari

Keyword(s):

Bronchopulmonary Dysplasia ◽

Cell Types ◽

Premature Neonate ◽

Respiratory Disorder ◽

Immune Mediators ◽

Pulmonary Disorder ◽

Postmenstrual Age ◽

Endothelial Integrity ◽

Physiologic Role

Bronchopulmonary dysplasia, or BPD, is a chronic pulmonary disorder of premature infants, commonly defined as having an oxygen requirement at 36 weeks postmenstrual age. It is an important source of morbidity and mortality in premature neonates. Its’ etiology appears to be multifactorial with the most common associations being prematurity, need for mechanical ventilation, and oxygen exposure. Implied in the pathogenesis of BPD is the role of cytokines which are immune mediators produced by most cell types. This is evidenced by studies in which there exist alterations in the levels of “pro-inflammatory” and “anti-inflammatory” cytokines. The imbalance of these cytokines have either heralded the onset or predicted the presence of BPD, or indicated a decreased propensity to developing this chronic respiratory disorder of preterm infants. Many other pulmonary markers have been shown to be altered in patients with BPD. These include markers indicative of altered lung repair processes, decreased endothelial integrity, oxidative damage and abnormal fibrinolytic activity, all of which are thought to be mechanisms contributing to the development of BPD. In this review, we will discuss the physiologic role of specific biomarkers in the pulmonary tract of the human premature neonate, the perturbations that enable them to be deranged, and their proposed association with BPD.

Download Full-text

The Pertinent Role of Cell and Matrix Mechanics in Cell Adhesion and Migration

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.720494 ◽

2021 ◽

Vol 9 ◽

Author(s):

Claudia Tanja Mierke

Keyword(s):

Cell Adhesion ◽

Matrix Mechanics ◽

Cell Adhesion And Migration ◽

And Migration

Download Full-text

Determinants of platelet kinetics: effects of pulmonary microembolism

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.4.1716 ◽

1988 ◽

Vol 65 (4) ◽

pp. 1716-1722 ◽

Cited By ~ 2

Author(s):

B. K. McCandless ◽

J. E. Kaplan ◽

J. A. Cooper ◽

A. B. Malik

Keyword(s):

Tranexamic Acid ◽

Vascular Injury ◽

Half Life ◽

Initial Increase ◽

Fibrin Deposition ◽

Subendothelial Matrix

We examined the mechanisms of platelet uptake in the lungs after alpha-thrombin-induced pulmonary microembolism. Platelets labeled with 111In-oxine were reinfused into chronically prepared sheep. Pulmonary microembolism resulted in an increase in lung platelet radioactivity (95.5 +/- 15.3%; n = 4), which was followed by an exponential washout (half-life = 115 +/- 4 min). Platelet uptake in the lungs was more sustained after prior fibrinolytic inhibition with tranexamic acid (half-life = 178 +/- 11 min), although the initial increase was similar (90.7 +/- 9.6%; n = 7). Prior depletion of fibrinogen with ancrod (Arvin), blunted the initial increase in lung platelet uptake after alpha-thrombin challenge (31.7 +/- 11.3%, n = 5), indicating that the effect of thrombin was markedly dependent on fibrinogen. We examined the role of circulating granulocytes, since platelets may bind to subendothelial matrix exposed after granulocyte-mediated lung vascular injury. Maximal pulmonary platelet uptake after thrombin in granulocytopenic sheep was not different from control (71.7 +/- 14.4%; n = 4). The results indicate that pulmonary microembolism results in lung platelet sequestration. Platelet uptake is not dependent on granulocyte-mediated vascular injury but requires fibrin deposition and is sustained if fibrinolysis is inhibited.

Download Full-text

Visualizability and Intelligibility

10.1093/oso/9780190652913.003.0007 ◽

2017 ◽

Author(s):

Henk W. de Regt

Keyword(s):

Quantum Physics ◽

Niels Bohr ◽

Wave Mechanics ◽

Classical Physics ◽

Matrix Mechanics ◽

Contextual Theory ◽

Erwin Schrödinger ◽

Gradual Loss ◽

Depth Study

This chapter investigates the relation between visualizability and intelligibility, by means of an in-depth study of the transition from classical physics to quantum physics in the first decades of the twentieth century. In this development, the issue of visualizability played a central role. After a brief discussion of the visualizability of classical physics, it examines the gradual loss of visualizability in quantum theory, focusing on the work of quantum physicists Niels Bohr, Wolfgang Pauli, Werner Heisenberg, and Erwin Schrödinger. The chapter presents a detailed analysis of the role of visualizability (Anschaulichkeit) in the competition between Schrödinger’s wave mechanics and Heisenberg’s matrix mechanics, and in the discovery of electron spin. The contextual theory of understanding asserts that visualizability is one out of many possible tools for understanding, albeit one that has proved to be very effective in science. This conclusion is supported by an analysis of the role of visualization in postwar quantum physics, especially via Feynman diagrams.

Download Full-text

The role of sphingolipids in endothelial barrier function

Biological Chemistry ◽

10.1515/hsz-2014-0305 ◽

2015 ◽

Vol 396 (6-7) ◽

pp. 681-691 ◽

Cited By ~ 12

Author(s):

Peter L. Jernigan ◽

Amy T. Makley ◽

Richard S. Hoehn ◽

Michael J. Edwards ◽

Timothy A. Pritts

Keyword(s):

Barrier Function ◽

Biologically Active ◽

Endothelial Barrier ◽

Endothelial Barrier Function ◽

Physiologic Function ◽

Sphingosine 1 Phosphate ◽

Endothelial Integrity ◽

Pathologic Processes ◽

Immense Potential

Abstract Sphingolipids are a ubiquitous family of essential lipids with an increasingly understood role as biologically active mediators in numerous physiologic and pathologic processes. Two particular sphingolipid species, sphingosine-1-phosphate and ceramide, and their metabolites interact both directly and indirectly with endothelial cells to regulate vascular permeability. Sphingosine-1-phosphate generally augments endothelial integrity while ceramide tends to promote vascular leak, and a tight balance between the two is necessary to maintain normal physiologic function. The mechanisms by which sphingolipids regulate endothelial barrier function are complex and occur through multiple different pathways, and disruptions or imbalances in these pathways have been implicated in a number of specific disease processes. With improved understanding of sphingolipid biology, endothelial function, and the interactions between the two, several targets for therapeutic intervention have emerged and there is immense potential for further advancement in this field.

Download Full-text

C5b-9 membrane attack complex mediates endothelial cell apoptosis in experimental glomerulonephritis

AJP Renal Physiology ◽

10.1152/ajprenal.2000.278.5.f747 ◽

2000 ◽

Vol 278 (5) ◽

pp. F747-F757 ◽

Cited By ~ 47

Author(s):

Jeremy Hughes ◽

Masaomi Nangaku ◽

Charles E. Alpers ◽

Stuart J. Shankland ◽

William G. Couser ◽

...

Keyword(s):

Endothelial Cell ◽

Regulatory Protein ◽

Membrane Attack Complex ◽

Fold Increase ◽

Renal Perfusion ◽

Con A ◽

Immune Mediated ◽

The Right ◽

Endothelial Integrity

We studied the role of the C5b-9 membrane attack complex in two models of inflammatory glomerulonephritis (GN) initiated by acute glomerular endothelial injury in Piebold-viral-Glaxo (PVG) complement-sufficient rats (C+), C6-deficient rats (C6−), and rats systematically depleted of complement with cobra venom factor (CVF). GN was induced by performing a left nephrectomy and selectively perfusing the right kidney with either 1) the lectin concanavalin A (Con A) followed by complement-fixing anti-Con A (Con A GN) or 2) purified complement-fixing goat anti-rat glomerular endothelial cell (GEN) antibody [immune-mediated thrombotic microangiopathy (ITM)]. Comparable levels of GEN apoptosis were detected in C+ animals in both models. CVF administration reduced GEN apoptosis by 10- to 12-fold. GEN apoptosis was C5b-9 dependent because PVG C6− rats were protected from GEN loss. Furthermore, functional inhibition of the cell surface complement regulatory protein CD59 by renal perfusion with anti-CD59 antibody in ITM resulted in a 3.5-fold increase in GEN apoptosis. Last, in Con A GN, abrogation of GEN apoptosis preserved endothelial integrity and renal function. This study demonstrates the specific role of C5b-9 in the induction of GEN apoptosis in experimental inflammatory GN, a finding with implications for diseases associated with the presence of antiendothelial cell antibodies.

Download Full-text