scholarly journals Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

2015 ◽  
Vol 2015 ◽  
pp. 1-23 ◽  
Author(s):  
Michael Schnoor ◽  
Pilar Alcaide ◽  
Mathieu-Benoit Voisin ◽  
Jaap D. van Buul
Keyword(s):  
Rheumatoid Arthritis ◽  
Current Knowledge ◽  
Leukocyte Adhesion ◽  
Vascular Wall ◽  
Point Of View ◽  
Regulatory Mechanisms ◽  
Integrin Receptors ◽  
Endothelial Monolayers ◽  
Leukocyte Extravasation ◽  
Endothelial Adhesion Molecules

Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

scholarly journals Endothelial function and its role in the formation of cardiovascular pathology in patients with rheumatoid arthritis

2019 ◽  
Vol 100 (3) ◽  
pp. 451-456
Author(s):  
A A Tulichev ◽  
N Yu Borovkova ◽  
N N Borovkov ◽  
A A Spassky ◽  
I V Polyakova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Unknown Origin ◽  
Vascular Wall ◽  
Cardiovascular Complications ◽  
Point Of View ◽  
Microvascular Changes ◽  
Initial Stage

Currently rheumatoid arthritis is considered as an immune inflammatory disease of unknown origin characterized by chronic erosive arthritis and systemic damage of internal organs, leading to early disability and reduced life expectancy. Cardiovascular diseases are most often mentioned as factors of poor prognosis in rheumatoid arthritis. Pathology of the cardiovascular system in rheumatoid arthritis is usually associated with the macro- and microvascular changes and rheumatoid lesions of the heart. The leading factor in the damage of the vascular wall in rheumatoid arthritis is systemic inflammation affecting its viscosity and elastic properties, increased rigidity, impaired endothelial function. Endothelial dysfunction is currently regarded to as an initial stage of morphogenesis of various vascular disorders. It is considered as a subclinical marker of cardiovascular diseases and the earliest predictor of cardiovascular complications. From this point of view study of endothelial dysfunction in patients with rheumatoid arthritis aimed at determining cardiovascular risk is a perspective direction. Only single and fragmentary information about certain endothelial functions in patients with rheumatoid arthritis and substances released in this. There is no clear analysis of relationship between them and dependence on the process activity. Not clear is their role in the pathology of the vascular wall in rheumatoid arthritis. This literature review discusses the problem of endothelial dysfunction in rheumatoid arthritis patients as well as its role in the development of cardiovascular diseases in these patients. The development mechanisms and the role of immune inflammation in its formation are considered. Also the association was found between chronic inflammatory activity indicators in rheumatoid arthritis and various biological markers and development of endothelial dysfunction. The effects of antirheumatic treatment on endothelial dysfunction in these patients were analyzed.

Pulmonary Manifestations in Rheumatoid Arthritis, Psoriatic Arthritis and Peripheral Spondyloarthritis Prevalence, Diagnostic Approach and Treatment Options

2020 ◽  
Vol 16 ◽  
Author(s):  
Daniel Dejcman ◽  
Valentin Sebastian Schäfer ◽  
Dirk Skowasch ◽  
Carmen Pizarro ◽  
Andreas Krause ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Lung Disease ◽  
Current Knowledge ◽  
Treatment Options ◽  
Pulmonary Diseases ◽  
Chronic Obstructive ◽  
Pulmonary Manifestations ◽  
Major Cluster ◽  
Peripheral Spondyloarthritis

: Interstitial lung disease (ILD) is the most common form of pulmonary impairment in patients with rheumatoid arthritis (RA). However, patients with RA or other arthritic diseases such as psoriatic arthritis (PsA) or peripheral spondyloarthritis (pSpA) may develop several other pulmonary diseases such as chronic obstructive lung disease (COPD) with a higher risk than patients without arthritis. The article at hand aims at summarizing the current knowledge on the prevalence of pulmonary diseases in the above-mentioned forms of arthritis, the challenges for prevalence studies and detecting pulmonary diseases in patients with arthritis as well as possible treatment options. Dyspnea, cough or other pulmonary symptoms or findings in arthritis patients should prompt gradual diagnostic procedures considering pulmonary manifestations as a major cluster of differential diagnosis. Considering its poor prognosis and morbidity burden, RA-ILD needs to be ruled out. Treatment of manifestations often lacks solid evidencebased guidelines and referrals to specialized centers are often necessary.

scholarly journals Glucose lowering by SGLT2-inhibitor empagliflozin accelerates atherosclerosis regression in hyperglycemic STZ-diabetic mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jan Pennig ◽  
Philipp Scherrer ◽  
Mark Colin Gissler ◽  
Nathaly Anto-Michel ◽  
Natalie Hoppe ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Plasma Cholesterol ◽  
Sglt2 Inhibitor ◽  
Vascular Wall ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Diabetic Mice ◽  
Glucose Lowering ◽  
Atherosclerosis Progression ◽  
Glucose Levels

AbstractDiabetes worsens atherosclerosis progression and leads to a defect in repair of arteries after cholesterol reduction, a process termed regression. Empagliflozin reduces blood glucose levels via inhibition of the sodium glucose cotransporter 2 (SGLT-2) in the kidney and has been shown to lead to a marked reduction in cardiovascular events in humans. To determine whether glucose lowering by empagliflozin accelerates atherosclerosis regression in a mouse model, male C57BL/6J mice were treated intraperitoneally with LDLR- and SRB1- antisense oligonucleotides and fed a high cholesterol diet for 16 weeks to induce severe hypercholesterolemia and atherosclerosis progression. At week 14 all mice were rendered diabetic by streptozotocin (STZ) injections. At week 16 a baseline group was sacrificed and displayed substantial atherosclerosis of the aortic root. In the remaining mice, plasma cholesterol was lowered by switching to chow diet and treatment with LDLR sense oligonucleotides to induce atherosclerosis regression. These mice then received either empagliflozin or vehicle for three weeks. Atherosclerotic plaques in the empagliflozin treated mice were significantly smaller, showed decreased lipid and CD68+ macrophage content, as well as greater collagen content. Proliferation of plaque resident macrophages and leukocyte adhesion to the vascular wall were significantly decreased in empagliflozin-treated mice. In summary, plasma glucose lowering by empagliflozin improves plaque regression in diabetic mice.

Postischemic Revascularization: From Cellular and Molecular Mechanisms to Clinical Applications

2013 ◽  
Vol 93 (4) ◽  
pp. 1743-1802 ◽  
Author(s):  
Jean-Sébastien Silvestre ◽  
David M. Smadja ◽  
Bernard I. Lévy
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Vascular Wall ◽  
Arterial Disease ◽  
Cellular Mechanisms ◽  
Collateral Growth ◽  
Vessel Growth ◽  
Ischemic Diseases

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

scholarly journals Nitric oxide function in atherosclerosis

1997 ◽  
Vol 6 (1) ◽  
pp. 3-21 ◽  
Author(s):  
K. E. Matthys ◽  
H. Bult
Keyword(s):  
Nitric Oxide ◽  
Leukocyte Adhesion ◽  
Atherosclerotic Lesion ◽  
Vascular Wall ◽  
Early Event ◽  
No Production ◽  
Oxygen Intermediates ◽  
Atherosclerotic Lesions ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates.

scholarly journals Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4942
Author(s):  
Maria Grazia Ronga ◽  
Marco Cavallone ◽  
Annalisa Patriarca ◽  
Amelia Maia Leite ◽  
Pierre Loap ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Current Knowledge ◽  
High Energy ◽  
High Dose Rate ◽  
Point Of View ◽  
High Dose ◽  
Dose Rates ◽  
High Energy Electrons ◽  
Very High Energy ◽  
Very High

The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts.

scholarly journals Assessment of calcium antagonist therapy protective effect on the thickness of the intima-media complex in patients with arterial hypertension

2021 ◽  
Vol 10 (2) ◽  
pp. 54-57
Author(s):  
N. I. Morozova ◽  
T. A. Mulerova
Keyword(s):  
Calcium Antagonist ◽  
Arterial Hypertension ◽  
Calcium Antagonists ◽  
Vascular Wall ◽  
Mthfr Gene ◽  
Point Of View ◽  
Enos Gene ◽  
Polymerase Chain ◽  
Atherosclerotic Process ◽  
Agt Gene

Aim. To evaluate the connection of calcium antagonist (amlodipine) therapy with the dynamics of the intima-media complex thickness in patients with arterial hypertension (AH), depending on genetic polymorphism.Methods. The study included representatives of the indigenous nationality (the Shors) – 901 people, of which a group of 367 people with hypertension was identified. The prospective stage of observation included 234 people who did not receive antihypertensive therapy. Based on the prescription of calcium antagonists, patients with hypertension were divided into two groups. Gene polymorphism was tested by polymerase chain reaction.Results. In the Shor cohort, the regression of the intima-media complex thickness of the carotid arteries was observed more often in hypertensive patients who received calcium antagonists if to compare them with those who did not take the drug [OR = 2.30]. In addition, the decrease in the atherosclerotic process is associated with the genotype carriage: I/I of the ACE gene [OR = 9.42], T/C of the AGT gene [OR = 3.52], 4b/4b and 4b/4a of the eNOS gene [OR = 2.26 and OR = 3.75], C/C of the MTHFR gene [OR = 2.62].Conclusion. Pharmacogenetic aspects are valuable from the point of view of an individual approach and obtaining the most pronounced pharmacological response in order to slow down the processes of vascular wall remodeling in patients with hypertension. 

scholarly journals Etiology and Risk Factors for Rheumatoid Arthritis: A State-of-the-Art Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Vasco C. Romão ◽  
João Eurico Fonseca
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Disease Risk ◽  
State Of The Art ◽  
Current Knowledge ◽  
Epidemiological Studies ◽  
Complex Interactions ◽  
Significant Burden ◽  
Risk Of Disease ◽  
Societal Level

Rheumatoid arthritis (RA) is the most common systemic inflammatory rheumatic disease. It is associated with significant burden at the patient and societal level. Extensive efforts have been devoted to identifying a potential cause for the development of RA. Epidemiological studies have thoroughly investigated the association of several factors with the risk and course of RA. Although a precise etiology remains elusive, the current understanding is that RA is a multifactorial disease, wherein complex interactions between host and environmental factors determine the overall risk of disease susceptibility, persistence and severity. Risk factors related to the host that have been associated with RA development may be divided into genetic; epigenetic; hormonal, reproductive and neuroendocrine; and comorbid host factors. In turn, environmental risk factors include smoking and other airborne exposures; microbiota and infectious agents; diet; and socioeconomic factors. In the present narrative review, aimed at clinicians and researchers in the field of RA, we provide a state-of-the-art overview of the current knowledge on this topic, focusing on recent progresses that have improved our comprehension of disease risk and development.

Sign in / Sign up

Export Citation Format

Share Document