Relation of Cytokine Profile to Clinical and Hemodynamic Features in Young Patients With Congenital Heart Disease and Pulmonary Hypertension

Zorzanelli, Leína; Maeda, Nair Yukie; Clavé, M; Thomaz, Ana Maria; Galas, Filomena Regina Barbosa Gomes; Rabinovitch, Marlene; Lopes, Antônio Augusto

doi:10.1016/j.amjcard.2016.09.020

Cited by 14 publications

(12 citation statements)

References 25 publications

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“… 147 Conversely, soluble ICAM-1 levels decreased when young patients with CHD and PH were treated with the phosphodiesterase 5 inhibitor sildenafil. 148 Interestingly, ICAM-1 expression on pulmonary arterial but not microvascular endothelial cells can be increased when endothelial cells are exposed to microparticles isolated from PH rats. 149 In line with their proposed role as disseminators of inflammatory signaling in the lung, 150 circulating microparticles may thus specifically promote inflammatory responses in the pulmonary arterial compartment in PAH.…”

Section: The Endothelium In Inflammation and Immunitymentioning

confidence: 96%

Inflammation and autoimmunity in pulmonary hypertension: is there a role for endothelial adhesion molecules? (2017 Grover Conference Series)

2018

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While pulmonary hypertension (PH) has traditionally not been considered as a disease that is directly linked to or, potentially, even caused by inflammation, a rapidly growing body of evidence has demonstrated the accumulation of a variety of inflammatory and immune cells in PH lungs, in and around the wall of remodeled pulmonary resistance vessels and in the vicinity of plexiform lesions, respectively. Concomitantly, abundant production and release of various inflammatory mediators has been documented in both PH patients and experimental models of PH. While these findings unequivocally demonstrate an inflammatory component in PH, they have fueled an intense and presently ongoing debate as to the nature of this inflammatory aspect: is it a mere bystander of or response to the actual disease process, or is it a pathomechanistic contributor or potentially even a trigger of endothelial injury, smooth muscle hypertrophy and hyperplasia, and the resulting lung vascular remodeling? In this review, we will discuss the present evidence for an inflammatory component in PH disease with a specific focus on the potential role of the endothelium in this scenario and highlight future avenues of experimental investigation which may lead to novel therapeutic interventions.

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Section: The Endothelium In Inflammation and Immunitymentioning

confidence: 96%

Inflammation and autoimmunity in pulmonary hypertension: is there a role for endothelial adhesion molecules? (2017 Grover Conference Series)

2018

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“…There was no difference in the median value of in the group with schistosomiasis-associated PAH compared to those without (152.3 pg/mL vs. 131.8 pg/mL, p = 0.177). Zorzanelli et al [34] disclosed that IL-13 was closely related to the age of the pediatric patients with PAH (r = 0.33, p = 0.022). In addition, in an established pulmonary vascular remodeling and PAH mouse model induced by Schistosoma mansoni, Crosby et al [35] found the degree of vascular remodeling correlated with proximity to granulomas.…”

Section: Il-13 and Its Receptors Il-13mentioning

confidence: 99%

Interleukin-13 in the pathogenesis of pulmonary artery hypertension

Yuan

2019

Journal of Laboratory Medicine

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Background Interleukin (IL)-13 is a regulatory factor of tissue remodeling and is involved in the pathogenesis of pulmonary artery hypertension (PAH). However, the implications of IL-13 in PAH remains uncertain. This article aims to describe the current knowledge on production and function of IL-13 and its receptors in the mechanisms of PAH. Content The study materials of this article were based on comprehensive literature retrieval of publications of IL-13 in PAH. These study materials were carefully reviewed, analyzed and discussed. Summary IL-13 levels in blood and lung tissue were elevated in both animal models of PAH and patients with PAH in comparison to non-PAH controls. Types I and II IL-13 receptors participate in pulmonary artery remodeling through signal transducer and activator of transcription (STAT)6 or through phosphatidylinositol 3-kinase (PI3K), STAT3 and mitogen activated protein kinase (MAPK) pathways. Oxidant, arginase 2 (Arg2) and hypoxia-inducible factor 1α are involved in the proliferation of pulmonary artery smooth muscle cells. Outlook Types I and II IL-13 receptors play an important role in the IL-13 signaling by STAT6 via Janus kinase kinases, and by PI3K, STAT3 and MAPK pathways, respectively. Alternative pathways, including oxidant, Arg2 and hypoxia-inducible factor 1α might be also involved in the pathological process of PAH development. Investigational therapies by inflammatory suppression or thrombolytic and anticoagulant agents could inhibit intimal hyperplasia of the pulmonary arteries and suppress pulmonary vasculature remodeling. Drug research and development oriented by this hypothesis would confer benefits to the treatment of PAH.

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“…Mediated by the hypothalamo-pituitary-adrenal axis, this inflammatory processes is intimately linked with overweight, obesity, and abdominal fat and its sequelae of comorbidities including risk factors for cardiovascular disease and coronary artery disease [49]. Inflammation may play an early role in altered vascular dynamics as inflammatory cytokines are elevated in young children with CHD [50]. For example, in young children with CHD (up to 3 years), circulating inflammatory cytokines (macrophage migration inhibitory factor chemokine, T-cells, interleukin-17 and Th2 immune response mediator) are positively correlated with the severity of the disease, and with pulmonary vascular resistance and congestion [50].…”

Section: A Mechanistic Link Between Waist Circumference and Cardiovasmentioning

confidence: 99%

“…Inflammation may play an early role in altered vascular dynamics as inflammatory cytokines are elevated in young children with CHD [50]. For example, in young children with CHD (up to 3 years), circulating inflammatory cytokines (macrophage migration inhibitory factor chemokine, T-cells, interleukin-17 and Th2 immune response mediator) are positively correlated with the severity of the disease, and with pulmonary vascular resistance and congestion [50]. Physical activity is known to decrease adiposity and BMI, and markers of stress and chronic inflammation, and to mitigate the association between stress and adiposity in otherwise healthy children [51][52][53][54].…”

Section: A Mechanistic Link Between Waist Circumference and Cardiovasmentioning

confidence: 99%

A cardiovascular disease risk factor in children with congenital heart disease: unmasking elevated waist circumference - a CHAMPS* study *CHAMPS: Children’s Healthy-Heart Activity Monitoring Program in Saskatchewan

Barbour-Tuck

Boyes

Tomczak

et al. 2020

BMC Cardiovasc Disord

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Background: Children with congenital heart disease (CHD) have an elevated risk of future cardiovascular disease but the underlying mechanisms are unclear. Abdominal obesity (measured as waist circumference) is a risk factor for adult onset of cardiovascular diseases and is correlated with low physical activity levels, commonly found in children with congenital heart disease. Elevated waist circumference may be a mechanism by which cardiovascular disease risk is elevated in children with CHD. The purpose of this study was to compare waist circumference between children with and without CHD, while considering potential confounders. We hypothesized that children with CHD would have higher measures of waist circumference when controlling for differences in birthweight, lean mass, and physical activity. Methods: Thirty-two children with CHD (10.9 ± 2.6 years; 12 female) from the Children's Healthy-Heart Activity Monitoring Program in Saskatchewan, and 23 healthy controls (11.7 ± 2.5 years; 10 female) were studied. Waist circumference, physical activity (physical activity questionnaire), body composition (lean mass; dual x-ray absorptiometry), and birthweight were assessed. Analysis of covariance, Mann-Whitney U, and independent sample t-tests were used to assess group differences (p < 0.05). Results: Children with CHD had greater waist circumference than controls, controlling for lean mass, physical activity, birthweight, and sex (F (1, 49) = 4.488, p = 0.039). Physical activity, lean mass, and birthweight were not significantly different between groups (p > 0.05). Conclusion: Our findings generate a novel hypothesis-higher waist circumferences in children with CHD compared to age-matched controls, may contribute to an elevated risk of cardiovascular disease.

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Relation of Cytokine Profile to Clinical and Hemodynamic Features in Young Patients With Congenital Heart Disease and Pulmonary Hypertension

Cited by 14 publications

References 25 publications

Inflammation and autoimmunity in pulmonary hypertension: is there a role for endothelial adhesion molecules? (2017 Grover Conference Series)

Inflammation and autoimmunity in pulmonary hypertension: is there a role for endothelial adhesion molecules? (2017 Grover Conference Series)

Interleukin-13 in the pathogenesis of pulmonary artery hypertension

A cardiovascular disease risk factor in children with congenital heart disease: unmasking elevated waist circumference - a CHAMPS* study *CHAMPS: Children’s Healthy-Heart Activity Monitoring Program in Saskatchewan

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