The mediating role of vascular inflammation in traffic-related air pollution associated changes in insulin resistance in healthy adults

Abstract BackgroundEpidemiological evidence supports that ambient air pollution exposure is associated with the onset of clinically overt diabetes, but the precise pathways are unknown. This study aimed to investigate whether dysfunctional bone-vascular axis can be a mechanistic linkage between air pollution and insulin resistance.MethodsStudy outcomes were determined by assessing a series of circulating biomarkers indicative of bone-vascular axis, insulin resistance, and immune inflammation among 73 healthy adults who undergo repeated clinical visits in Beijing, China, 2014-2016. Linear mixed-effects models were used to evaluate the impacts of air pollution on outcomes, and the potential interlinked pathways between exposure measures and insulin resistance were examined using mediation analyses.ResultsParticipants experienced extremely high levels of ambient particulates and gaseous pollutants exposures throughout the study, with daily concentrations varying from 30.6 to 236.2 μg/m3 for fine particulate matter (PM2.5) and 54.9 to 235.8 μg/m3 for oxides of nitrogen. We observed that short-term exposure to air pollutants was associated with changes in biomarkers of the bone-vascular axis and insulin resistance. Specifically, an interquartile range increase in 7-day moving average of PM2.5 concentrations was significantly associated with elevations of 30.1% in osteoprotegerin and 20.5% in adiponectin, as well as reductions of 16.6% in bone morphogenetic protein-4 and 8.5% in soluble insulin receptor ectodomain. Further, higher PM2.5 exposures were positively related to various indicators of immune inflammation, including elevations of 22.5% in interleukin-10, 19.6% in soluble CD163 and 27.5% in C-C chemokine ligand-2. Mediation analyses revealed that activation of the bone-vascular axis mediated up to 52% of pollutants-associated immune inflammatory responses, both of which could explain 66% of increases in insulin resistance attributed to pollutants exposures.ConclusionsShort-term air pollution exposure is potentially capable of promoting insulin resistance possibly via generating dysfunctional bone-vascular axis, suggesting a novel mechanism by which air pollution may potentiate the development of diabetes.

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Air Pollution and Adolescent Development: Evidence from a 3-Year Longitudinal Study in China

Children ◽

10.3390/children8110987 ◽

2021 ◽

Vol 8 (11) ◽

pp. 987

Author(s):

Na Ni ◽

Xinli Chi ◽

Wei Liu ◽

Xiumin Cui

Keyword(s):

Air Pollution ◽

Emotional Disorders ◽

Youth Development ◽

Adolescent Development ◽

Physical Environment ◽

Southern China ◽

Positive Development ◽

Mediating Role ◽

The Impact

This study aimed to investigate the impact of air pollution on the development of adolescents and the mediating role of students’ emotional disorders. Participants came from a longitudinal sample group of adolescents (n = 1301) in Southern China from the years 2016 to 2018. They were assessed for the Positive Youth Development and emotional disorders, and air pollution was measured by the Air Quality Index. The results show that students’ higher degree of exposure to air pollution was negatively associated with their positive development. Three out of four emotional disorders (i.e., anxiety, neuroticism, and withdrawal) mediate this association. The results suggest that the physical environment can have a paramount influence on the emotional status and overall development of adolescents, calling for intervention programs by policymakers.

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Methotrexate attenuates vascular inflammation through an adenosine-microRNA dependent pathway

eLife ◽

10.7554/elife.58064 ◽

2021 ◽

Vol 10 ◽

Author(s):

Dafeng Yang ◽

Stefan Haemmig ◽

Haoyang Zhou ◽

Daniel Pérez-Cremades ◽

Xinghui Sun ◽

...

Keyword(s):

Insulin Resistance ◽

Vascular Endothelium ◽

Vascular Inflammation ◽

Vascular Diseases ◽

High Dose ◽

Dependent Manner ◽

Diet Induced Obesity ◽

Therapeutic Opportunity ◽

Anti Inflammatory

Endothelial cell (EC) activation is an early hallmark in the pathogenesis of chronic vascular diseases. MicroRNA-181b (MiR-181b) is an important anti-inflammatory mediator in the vascular endothelium affecting endotoxemia, atherosclerosis, and insulin resistance. Herein, we identify that the drug methotrexate (MTX) and its downstream metabolite adenosine exert anti-inflammatory effects in the vascular endothelium by targeting and activating MiR-181b expression. Both systemic and endothelial-specific MiR-181a2b2-deficient mice develop vascular inflammation, white adipose tissue (WAT) inflammation, and insulin resistance in a diet-induced obesity model. Moreover, MTX attenuated diet-induced WAT inflammation, insulin resistance, and EC activation in a MiR-181a2b2-dependent manner. Mechanistically, MTX attenuated cytokine-induced EC activation through a unique adenosine-adenosine receptor A3-SMAD3/4-MiR-181b signaling cascade. These findings establish an essential role of endothelial MiR-181b in controlling vascular inflammation and that restoring MiR-181b in ECs by high dose MTX or adenosine signaling may provide a potential therapeutic opportunity for anti-inflammatory therapy.

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