In Vitro Investigation of Vascular Permeability in Endothelial Cells from Human Artery, Vein and Lung Microvessels at Steady-State and Anaphylactic Conditions

Callesen, Katrine T; Yuste-Montalvo, Alma; Poulsen, Lars K.; Jensen, Bettina M.; Esteban, Vanesa

doi:10.3390/biomedicines9040439

Cited by 11 publications

(11 citation statements)

References 20 publications

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“…ECs form a monolayer called endothelium that functions as the physical barrier between blood and tissues regulating vascular permeability and blood pressure [115,[138][139][140]. In anaphylaxis, mediators released during the reaction causes the opening of adherent junctions giving rise to an increase in vascular permeability and stimulating fluid extravasation [58,115].…”

Section: Cells and Processesmentioning

confidence: 99%

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

Fernández-Bravo¹,

Palacio-Garcia²,

Requena-Robledo³

et al. 2022

J Investig Allergol Clin Immunol

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The life-threating nature of the anaphylactic reactions promotes a growing interest to discover new biomarkers that could support their better diagnosis and prevention. However, both the clinical features and the etiopathology of anaphylaxis are very diverse, hindering the elucidation of valuable molecular indicators of disease. Most studies of anaphylaxis have focused on the immune system. Precisely, anaphylactic reactions are characterized primarily by IgE-mediated activation of mast cells and basophils and the release of several mediators. Among them, determinations of the serum tryptase levels is the main in vitro test used to confirm the reaction and there are no available biomarkers with predictive capacity for this pathological event. However, recent research has postulated that alternative pathways, cell types and systems are involved. Consequently, different molecular products have been explored and indicated as potential biomarkers, but none of them have been translated into the clinical practice yet. Precisely, vasoactive agents, proteases, proteoglycans, lipids, interleukins, cytokines, products of the complement-contact and coagulation systems, circulating proteins, extracellular vesicles, microRNAs and metabolites have been found to be altered in patients with anaphylaxis. The recognition of biological processes and molecular pathways interacting in the magnitude of the microenvironments switched on in anaphylaxis will notably nourish the clinical practice and the recognition of better molecular markers. Therefore, this article covers a broad review of the different mediators described in anaphylaxis and their proposal as biomarkers of this pathological event, as well as their role in the molecular basis of the reaction.

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Section: Cells and Processesmentioning

confidence: 99%

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

Fernández-Bravo¹,

Palacio-Garcia²,

Requena-Robledo³

et al. 2022

J Investig Allergol Clin Immunol

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“…Primary cultures of vascular smooth muscle cells were obtained from a whole aortic arterial segment of patient undergoing cardiac surgery (HA-VSMC) according to previously described [ 14 ]. The arterial segment was cleaned and cut into small pieces.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting

et al. 2021

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Atherosclerosis is the predominant pathology associated to premature deaths due to cardiovascular disease. However, early intervention based on a personalized diagnosis of cardiovascular risk is very limited. We have previously identified metabolic alterations during atherosclerosis development in a rabbit model and in subjects suffering from an acute coronary syndrome. Here we aim to identify specific metabolic signatures which may set the basis for novel tools aiding cardiovascular risk diagnosis in clinical practice. In a cohort of subjects with programmed coronary artery bypass grafting (CABG), we have performed liquid chromatography and targeted mass spectrometry analysis in urine and plasma. The role of vascular smooth muscle cells from human aorta (HA-VSMCs) was also investigated by analyzing the intra and extracellular metabolites in response to a pro-atherosclerotic stimulus. Statistically significant variation was considered if p value < 0.05 (Mann-Whitney test). Urinary trimethylamine N-oxide (TMAO), arabitol and spermidine showed higher levels in the CVrisk group compared with a control group; while glutamine and pantothenate showed lower levels. The same trend was found for plasma TMAO and glutamine. Plasma choline, acetylcholine and valine were also decreased in CVrisk group, while pyruvate was found increased. In the secretome of HA-VSMCs, TMAO, pantothenate, glycerophosphocholine, glutathion, spermidine and acetylcholine increased after pro-atherosclerotic stimulus, while secreted glutamine decreased. At intracellular level, TMAO, pantothenate and glycerophosphocholine increased with stimulation. Observed metabolic deregulations pointed to an inflammatory response together with a deregulation of oxidative stress counteraction.

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“…Another interesting study carried out in mice determined that histamine-induced vascular permeability associated with anaphylaxis occurs in postcapillary venules ( 166 ). Furthermore, a recent investigation focusing on humans has shown the relevance of micro-ECs as the sole responders to anaphylactic mediators in in vitro vascular permeability ( 167 ). The high extravasation of fluid contributes to edema of the airways and pulmonary emphysema ( 168 ).…”

Section: Cardiovascular Pathophysiology Of Anaphylaxismentioning

confidence: 99%

Pathophysiological, Cellular, and Molecular Events of the Vascular System in Anaphylaxis

et al. 2022

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Anaphylaxis is a systemic hypersensitivity reaction that can be life threatening. Mechanistically, it results from the immune activation and release of a variety of mediators that give rise to the signs and symptoms of this pathological event. For years, most of the research in anaphylaxis has focused on the contribution of the immune component. However, approaches that shed light on the participation of other cellular and molecular agents are necessary. Among them, the vascular niche receives the various signals (e.g., histamine) that elicit the range of anaphylactic events. Cardiovascular manifestations such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and cardiac alterations are crucial in the pathophysiology of anaphylaxis and are highly involved to the development of the most severe cases. Specifically, the endothelium, vascular smooth muscle cells, and their molecular signaling outcomes play an essential role downstream of the immune reaction. Therefore, in this review, we synthesized the vascular changes observed during anaphylaxis as well as its cellular and molecular components. As the risk of anaphylaxis exists both in clinical procedures and in routine life, increasing our knowledge of the vascular physiology and their molecular mechanism will enable us to improve the clinical management and how to treat or prevent anaphylaxis.Key MessageAnaphylaxis, the most severe allergic reaction, involves a variety of immune and non-immune molecular signals that give rise to its pathophysiological manifestations. Importantly, the vascular system is engaged in processes relevant to anaphylactic events such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and decreased cardiac output. The novelty of this review focuses on the fact that new studies will greatly improve the understanding of anaphylaxis when viewed from a vascular molecular angle and specifically from the endothelium. This knowledge will improve therapeutic options to treat or prevent anaphylaxis.

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In Vitro Investigation of Vascular Permeability in Endothelial Cells from Human Artery, Vein and Lung Microvessels at Steady-State and Anaphylactic Conditions

Cited by 11 publications

References 20 publications

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting

Pathophysiological, Cellular, and Molecular Events of the Vascular System in Anaphylaxis

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