Sex differences in the redox response to fine particulate matter (PM) air pollution protects female mice against metabolic and cardiac injury.

Fine particulate matter (PM) exposure increases the cardiometabolic disease risk. While there is extensive research on how PM impairs cardiometabolic health in male mice, its health impact is largely unexplored in females. To examine PM-induced cardiometabolic effects in females, female and male mice (n = 10/group) on a regular (12 h:12 h, RLC) or disturbed (18 h:6 h, DLC) light-dark cycle were exposed to concentrated ambient PM (CAP) for 30 days.

Inhalation of concentrated ambient PM2.5 promotes inactivation of telomerase reverse transcriptase, telomere shortening, and senescence of multiple cell types in mice.

Although some prior studies have identified an association between exposure to fine air-borne particulate matter (PM2.5) and indices of aging, the extent of these associations and their underlying mechanisms are uncertain. In this study, we exposed male C57BL/6J mice to filtered air and concentrated ambient PM2.

Aldose Reductase (AR) Mediates and Perivascular Adipose Tissue (PVAT) Modulates Endothelial Dysfunction of Short-Term High-Fat Diet Feeding in Mice.

Increased adiposity of both visceral and perivascular adipose tissue (PVAT) depots is associated with an increased risk of diabetes and cardiovascular disease (CVD). Under healthy conditions, PVAT modulates vascular tone via the release of PVAT-derived relaxing factors, including adiponectin and leptin. However, when PVAT expands with high-fat diet (HFD) feeding, it appears to contribute to the development of endothelial dysfunction (ED).

Fine particulate matter (PM)-induced pulmonary oxidative stress contributes to increases in glucose intolerance and insulin resistance in a mouse model of circadian dyssynchrony.

Results of human and animal studies independently suggest that either ambient fine particulate matter (PM) air pollution exposure or a disturbed circadian rhythm (circadian dyssynchrony) are important contributing factors to the rapidly evolving type-2-diabetes (T2D) epidemic. The objective of this study is to investigate whether circadian dyssynchrony increases the susceptibility to PM and how PM affects metabolic health in circadian dyssynchrony. We examined systemic and organ-specific changes in glucose homeostasis and insulin sensitivity in mice maintained on a regular (12/12 h light/dark) or disrupted (18/6 h light/dark, light-induced circadian dyssynchrony, LICD) light cycle exposed to air or concentrated PM (CAP, 6 h/day, 30 days).

Fine Particulate Matter (PM2.5)-Induced Pulmonary Oxidative Stress Contributes to Changes in the Plasma Lipidome and Liver Transcriptome in Mice.

Fine particulate matter (PM2.5) air pollution exposure increases the cardiovascular disease risk. Although the specific mechanisms remain elusive, it is thought that PM2.

Exposure to Fine Particulate Matter Air Pollution Alters mRNA and miRNA Expression in Bone Marrow-Derived Endothelial Progenitor Cells from Mice.

Exposure to fine particulate matter (PM) air pollution is associated with quantitative deficits of circulating endothelial progenitor cells (EPCs) in humans. Related exposures of mice to concentrated ambient PM (CAP) likewise reduces levels of circulating EPCs and induces defects in their proliferation and angiogenic potential as well. These changes in EPC number or function are predictive of larger cardiovascular dysfunction.

Fine particulate matter air pollution and aortic perivascular adipose tissue: Oxidative stress, leptin, and vascular dysfunction.

Exposure to fine particulate matter (PM ) air pollution increases blood pressure, induces vascular inflammation and dysfunction, and augments atherosclerosis in humans and rodents; however, the understanding of early changes that foster chronic vascular disease is incomplete. Because perivascular adipose tissue (PVAT) inflammation is implicated in chronic vascular diseases, we investigated changes in aortic PVAT following short-term air pollution exposure. Mice were exposed to HEPA-filtered or concentrated ambient PM (CAP) for 9 consecutive days, and the abundance of inflammatory, adipogenic, and adipokine gene mRNAs was measured by gene array and qRT-PCR in thoracic aortic PVAT.

Fine particulate matter (PM) inhalation-induced alterations in the plasma lipidome as promoters of vascular inflammation and insulin resistance.

Fine particulate matter (PM) air pollution exposure increases the risk of developing cardiovascular disease (CVD). Although the precise mechanisms by which air pollution exposure increases CVD risk remain uncertain, research indicates that PM-induced endothelial dysfunction contributes to CVD risk. Previous studies demonstrate that concentrated ambient PM (CAP) exposure induces vascular inflammation and impairs insulin and vascular endothelial growth factor (VEGF) signaling dependent on pulmonary oxidative stress.

Endothelial progenitor cells as critical mediators of environmental air pollution-induced cardiovascular toxicity.

Environmental air pollution exposure is a leading cause of death worldwide, and with increasing industrialization and urbanization, its disease burden is expected to rise even further. The majority of air pollution exposure-associated deaths are linked to cardiovascular disease (CVD). Although ample research demonstrates a strong correlation between air pollution exposure and CVD risk, the mechanisms by which inhalation of polluted air affects cardiovascular health are not completely understood.

Carnosine Supplementation Mitigates the Deleterious Effects of Particulate Matter Exposure in Mice.

Background Exposure to fine airborne particulate matter ( PM ) induces quantitative and qualitative defects in bone marrow-derived endothelial progenitor cells of mice, and similar outcomes in humans may contribute to vascular dysfunction and the cardiovascular morbidity and mortality associated with PM exposure. Nevertheless, mechanisms underlying the pervasive effects of PM are unclear and effective interventional strategies to mitigate against PM toxicity are lacking. Furthermore, whether PM exposure affects other types of bone marrow stem cells leading to additional hematological or immunological dysfunction is not clear.

Circadian toxicity of environmental pollution. Inhalation of polluted air to give a precedent.

Exposures to environmental stressors that derive from pollution (e.g. air, light) or lifestyle choices (e.

Glutathione S-transferase P deficiency induces glucose intolerance via JNK-dependent enhancement of hepatic gluconeogenesis.

Hepatic glutathione S-transferases (GSTs) are dysregulated in human obesity, nonalcoholic fatty liver disease, and diabetes. The multifunctional GST pi-isoform (GSTP) catalyzes the conjugation of glutathione with acrolein and inhibits c-Jun NH-terminal kinase (JNK) activation. Herein, we tested whether GSTP deficiency disturbs glucose homeostasis in mice.

Inhalation of Fine Particulate Matter Impairs Endothelial Progenitor Cell Function Via Pulmonary Oxidative Stress.

Objective: Exposure to fine particulate matter (PM) air pollution is associated with the depletion of circulating endothelial progenitor cells (EPCs), as well as vascular injury and dysfunction. Nevertheless, it remains unclear whether PM exposure leads to significant impairments in EPC function. Hence, we studied the effects of PM on EPC-mediated recovery of vascular perfusion after hindlimb ischemia and examined the mechanisms whereby PM exposure affects EPC abundance and function.

Biomarkers of Chronic Acrolein Inhalation Exposure in Mice: Implications for Tobacco Product-Induced Toxicity.

Exposure to tobacco smoke, which contains several harmful and potentially harmful constituents such as acrolein increases cardiovascular disease (CVD) risk. Although high acrolein levels induce pervasive cardiovascular injury, the effects of low-level exposure remain unknown and sensitive biomarkers of acrolein toxicity have not been identified. Identification of such biomarkers is essential to assess the toxicity of acrolein present at low levels in the ambient air or in new tobacco products such as e-cigarettes.

Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein.

Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100-275ppm, 10-30min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality.

Type 2 Diabetes Dysregulates Glucose Metabolism in Cardiac Progenitor Cells.

Type 2 diabetes is associated with increased mortality and progression to heart failure. Recent studies suggest that diabetes also impairs reparative responses after cell therapy. In this study, we examined potential mechanisms by which diabetes affects cardiac progenitor cells (CPCs).

Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress.

Background: Epidemiological evidence suggests that exposure to ambient air fine particulate matter (PM2.5) increases the risk of developing type 2 diabetes and cardiovascular disease. However, the mechanisms underlying these effects of PM2.

Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.

Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury.

Rationale: Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed.

Objective: We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury.

Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice.

High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice.

Acrolein decreases endothelial cell migration and insulin sensitivity through induction of let-7a.

Acrolein is a major reactive component of vehicle exhaust, and cigarette and wood smoke. It is also present in several food substances and is generated endogenously during inflammation and lipid peroxidation. Although previous studies have shown that dietary or inhalation exposure to acrolein results in endothelial activation, platelet activation, and accelerated atherogenesis, the basis for these effects is unknown.

Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response.

Excessive production of unsaturated aldehydes from oxidized lipoproteins and membrane lipids is a characteristic feature of cardiovascular disease. Our previous studies show that unsaturated lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) promote autophagy in rat aortic smooth muscle cells (RASMC). In this study, we examined the mechanism by which HNE induces autophagy.

Exposure to ambient air fine particulate matter prevents VEGF-induced mobilization of endothelial progenitor cells from the bone marrow.

Background: Exposure to ambient fine particulate matter air pollution (PM(2.5); < 2.5 µm in aerodynamic diameter) induces endothelial dysfunction and increases the risk for cardiovascular disease.