Ambient air pollution has become a common problem worldwide. Exposure to pollutant particles causes many health conditions, having a particular impact on pulmonary and cardiovascular disease. Increased understanding of the pathological processes related to these conditions may facilitate the prevention of the adverse impact of air pollution on our physical health.
Models | Exposure/Method | Results | Interpretation | References | ||
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Inflammation and Oxidative Stress | Coagulation and Adhesion Molecules | Morphology and Cell Proliferation | ||||
HUVECs | Vanadium oxide (V2O5) 3.12, 6.25, 12.5, 25 µg/cm2 for 1, 2, 3, 24, 48, 72 h |
↑ ROS at 25 µg/cm2 ↑ NO at 25 µg/cm2 (time-dependent) |
↑ VCAM-1 ↑ ICAM-1 ↑↑ PECAM-1 |
Morphology changed to fibroblast-like cells ↓ cell proliferation at 25 µg/cm2 ↑ annexin V, PI |
Exposure to V2O5 induced oxidative stress, enhanced the expression of adhesion molecules, and affected cell survival by diminishing cell proliferation, shape changes, and apoptosis. | [38] |
MH-S, Human alveolar macrophages |
PM (SRM 1649a) 10 µg/cm2 for 24 h |
# MH-S: ↑ IL-6 ↑ cAMP # Human alveolar macrophage: ↑ IL-6 |
β2AR encoding from the Adrb2 gene had an important role in PM-induced IL-6 release and activation of β2AR enhanced inflammatory response in both cell lines. | [44] | ||
PM (SRM 1649a) 10 µg/cm2 for 24 h Pretreated with β2AR agonist; albuterol 10−7 M |
↑↑ IL-6 | |||||
Alveolar macrophages from Adrb2−/− mice | PM (SRM 1649a) 10 µg/cm2 for 24 h Pretreated with β2AR agonist; albuterol 10−7 M |
↓ IL-6 | ||||
HUVECs, PBMC | PM (SRM 1648a) 62.5, 125, 250 and 500 µg/mL for 1, 4, 24, 48 h |
↑ MP (dose-, and time-dependent) ↑ intracellular Ca concentration |
↑ TF activity | PM-induced MP release, which, mediated by calcium mobilization, resulted in the prothrombotic state in both cell lines. | [45] | |
HUVECs | DEP 10–150 µg/mL for 16 h ±thrombin stimulation 1 U/mL |
# Without thrombin: ↓ tPA ↓ PAI-1 # With thrombin stimulation: ↔ tPA ↑ PAI-1 |
DEP enhanced arterial thrombus formation through decreased fibrinolytic function but did not affect cell survival. | [50] | ||
Venous blood of hamsters |
DEP (SRM 1650) 0.1, 0.5, 1, 5 µg/mL for 5 min |
↓ PFA100 closure time, dose-dependent |
DEP promoted thrombosis via platelet activation in a dose-dependent manner. | [46] | ||
Venous blood of TO mice |
DEP 1 µg/mL for 3 min |
↑ platelet aggregation ↓ PT ↓ PTT |
DEP promoted thrombosis by enhancing platelet aggregation and coagulation. | [47] | ||
Venous blood of TO mice |
DEP (SRM 2975) 0.1, 0.25, 0.5, 1 µg/mL for 3 min |
↑ platelet aggregation at 0.5 and 1 µg/mL, dose-dependent | DEP promoted thrombosis by enhancing platelet aggregation. | [48] | ||
Venous blood of TO mice Non-DM and DM mice |
DEP (SRM 2975) 0.25, 0.5, 1 µg/mL for 3 min |
# Non-DM mice: ↑ platelet aggregation at 1 µg/mL # DM mice: ↑↑ platelet aggregation, dose-dependent |
DEP promoted thrombosis by enhancing platelet aggregation, which was more obvious in DM mice. | [49] | ||
Venous blood of hamsters (Pfd Gold) |
Polystyrene particles: # 60 nm UFP - unmodified - carboxylated - amined at 1 or 3 µg/mL # 400 nm: Amine-polystyrene particles at 3 or 9 µg/mL for 5 min |
# Unmodified and carboxylated UFP: ↔ PFA100 closure time # Amine-UFP (60 nm): ↓ PFA100 closure time (3 µg/mL) # Amine-particles (400 nm): ↓ PFA100 closure time (9 µg/mL) |
Exposure to positively charged UFP (60 & 400 nm) augmented platelet function, leading to thrombosis. | [51] |
Models | Exposure/Method | Results | Interpretation | References | ||
---|---|---|---|---|---|---|
Inflammation and Oxidative Stress | Coagulation and Adhesion Molecules | Blood Parameters | ||||
Male Wistar rats 10–12 wk-old Cisplatin-induced AKI rats |
Intratracheal instillation of Cerium oxide nanoparticles (CeO2 NPs) 1 mg/kg |
Normal rats: # Kidney ↑ TNF-α, IL-6, GSH ↑ DNA damage # Lung tissue ↔ TNF-α, IL-6 ↓ catalase activity AKI rats: # Kidney ↑ TNF-α, IL-6, GSH ↑ DNA damage # Lung tissue ↑ TNF-α, IL-6 ↓ catalase activity |
Pulmonary exposure to CeO2 NPs induced inflammation and oxidative stress, and damaged DNA in the kidney. These effects were enhanced in kidney injury models. |
[57] | ||
Male mice C57Bl6/j 8–12 wk-old IL-6+/+ IL-6−/− |
Inhalation exposure to concentrated ambient particles (CAPs) from downtown Chicago for 8 h/d for 3 d Evaluate at 24 h after exposure |
# IL-6+/+ vs. non-PM): Lung tissue ↑ IL-6/18s mRNA ↑ SP-B/18s mRNA BALF ↑ IL-6 ↑ TNF-α ↑ MCP-1 # IL-6−/−: Lung tissue ↓ IL-6/18s mRNA ↓ SP-B/18s mRNA BALF ↓ IL-6 ↔ TNF-α ↔ MCP-1 |
# IL-6+/+ vs. non- PM): Lung tissue ↑ TF/18s mRNA Plasma ↑ TAT complexes White adipose tissue ↑ PAI-1/18s mRNA # IL-6−/−: Lung tissue ↓ TF/18s mRNA Plasma ↓ TAT complexes White adipose tissue ↔ PAI-1/18s mRNA |
Exposure to all types of PM could activate inflammatory response, coagulation system and inhibit fibrinolysis, resulting in a prothrombotic state. PM-induced coagulation through IL-6 production and blocking IL-6 signaling could alleviate the thrombotic process. |
[56] | |
Intratracheal instillation of urban PM (SRM1649a) 10, 100, 200 µg/animal Evaluate at 24 h after exposure |
# IL-6+/+ vs. non- PM): BALF ↑ protein ↑ macrophage, PMN ↑ IL-6 (dose-dependent) ↑ TNF-α # IL-6−/−: BALF ↔ protein ↔ macrophage, PMN ↓ IL-6 ↔ TNF-α |
# IL-6+/+ vs. non- PM): ↑ TF, ↑TF mRNA in lung tissue ↑ BALF D-dimer ↑ TAT complexes ↓ Bleeding time ↓ PT, ↓ PTT ↑ PAI-1/18s mRNA in the lung, adipose tissue ↑ PAI-1 in BALF # IL-6−/−: ↓ TF level, ↓TF mRNA in lung tissue ↓ BALF D-dimer ↓ TAT complexes ↔ PAI-1/18s mRNA in the lung, adipose tissue ↔ PAI-1 in BALF |
||||
Male mice (C57BL/6) 8–12 wk-old |
Inhalation exposure to concentrated ambient particles (CAPs) from downtown Chicago for 8 h/d for 3 d |
↑ NE in the lung, BAT, adrenal gland ↑ IL-6 in BALF |
↑ TAT complexes ↑ thrombus formation ↓ thrombotic occlusion time |
Inhalation of PM caused catecholamine release and promoted IL-6-mediated thrombosis. | [44] | |
Adrb1+/+Adrb2+/+ Adrb1−/−Adrb2+/+ Adrb1+/+Adrb2−/− Adrb1−/−Adrb2−/− |
Intratracheal instillation of urban PM (SRM1649a) 200 µg/animal Evaluate at 24 h after exposure |
BALF # Adrb1+/+Adrb2+/+ (vs. non-PM): ↑ IL-6 ↔ TNF-α, MCP-1 # Adrb1−/− Adrb2+/+ (vs. non-PM): ↑ IL-6 ↔ TNF-α, MCP-1 # Adrb1+/+Adrb2−/−: ↓ IL-6 ↔ TNF-α, MCP-1 # Adrb1−/−Adrb2−/−: ↓ IL-6 ↔ TNF-α, MCP-1 |
Plasma # Adrb1+/+Adrb2+/+ (vs. non-PM): ↑ TAT complexes ↓ thrombotic occlusion time # Adrb1−/− Adrb2+/+ (vs. non-PM): ↑ TAT complexes # Adrb1+/+Adrb2−/−: ↓ TAT complexes ↑ thrombotic occlusion time # Adrb1−/−Adrb2−/−: ↓ TAT complexes |
β2AR encoded by the Adrb2 gene in alveolar macrophages was necessary for PM-induced upregulation of IL-6, and enhanced susceptibility to thrombotic events. | ||
Adrb1+/+Adrb2+/+ Adrb1+/+Adrb2−/− |
Inhalation exposure to concentrated ambient particles (CAPs) from downtown Chicago for 8 h/d for 3 d |
# Adrb1+/+Adrb2−/−: ↓ IL-6/18s mRNA |
# Adrb1+/+Adrb2−/−: ↓ TAT complexes ↓ TF |
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Lyms-Cre Adrb2flox/flox mice (macrophage-specific deletion of β2AR) vs. Adrb2flox/flox |
Inhalation exposure to concentrated ambient particles (CAPs) from downtown Chicago for 8 h/d for 3 d Pretreated with formoterol (long-acting β2AR agonist) 1 × 10−5 M via inhalation twice every 12 h |
BALF # Adrb2flox/flox without formoterol: ↑ IL-6 in BALF # Adrb2flox/flox with formoterol: ↑↑ IL-6 # Lyms-Cre Adrb2flox/flox: ↓ IL-6 # Lyms-Cre Adrb2flox/flox with formoterol: ↓ IL-6 (vs. Adrb2flox/flox) ↔ IL-6 (vs. without formoterol) |
Plasma # Adrb2flox/flox without formoterol: ↑ TAT complexes ↑ factor II, TF mRNA ↓ thrombotic occlusion time # Adrb2flox/flox with formoterol: ↑ factor II, TF mRNA ↓ thrombotic occlusion time # Lyms-Cre Adrb2flox/flox: ↓ factor II, TF mRNA ↓ TAT complexes ↑ thrombotic occlusion time # Lyms-Cre Adrb2flox/flox with formoterol vs. Adrb2flox/flox: ↓ factor II, TF mRNA ↑ thrombotic occlusion time vs. without formoterol: ↔ factor II, TF mRNA ↔ thrombotic occlusion time |
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Male mice C57Bl6/j Old mice (20 mo-old) vs. Young mice (10 wk-old) |
Inhalation of ambient PM2.5 and PM10 at the roadside tunnel for 25–26 d (A) tunnel-filtered (B) tunnel-exposed in urban roadside tunnel (C) control in clean facility |
# Young mice (vs. non-PM): ↔ WBC in BALF # Old mice (vs. young mice) in clean air: ↑ WBC in BALF # Old mice (vs. young mice) with PM: ↔ WBC in BALF |
# Young mice (vs. non-PM): ↔ lung vWF ↔ plasma vWF ↓ lung TM ↑ P-selectin ↔ PF4 # Old mice (vs. young mice) in clean air: ↑ lung VWF ↑ plasma VWF ↔ lung TM ↑ P-selectin ↔ PF4 # Old mice (vs. young mice) with PM: ↑ lung vWF ↔ plasma VWF ↔ lung TM ↔ P-selectin ↔ PF4 |
# Young mice (vs. non-PM): ↑ RBC, Hb ↑ platelets ↔ WBC # Old mice (vs. young mice) in clean air: ↑ RBC, Hb ↑ platelets ↑ WBC # Old mice (vs. young mice) with PM: ↔ RBC, Hb ↔ platelets ↔ WBC |
Continuous inhalation of particulate matter air pollution triggered inflammatory response, and activated platelets, and endothelial cells. The older mice had higher inflammatory biomarkers at baseline, therefore the PM-mediated effects were not demonstrated in the old mice. |
[59] |
Male mice C57Bl6/j with spontaneous hypertension 11–12 wk-old |
Intratracheal instillation particulate matter # Road tunnel dust (RTD): 0.3, 1, 3, and 10 mg/kg # Urban dust (EHC-93) from Environmental Health Center in Ottawa, Canada 10 mg/kg Evaluation of lung tissue at 4, and 48 h after PM exposure |
# RTD (at 10 mg/kg): - at 4 h: ↑ TF ↑ thrombus formation - at 48 h: ↑ TF ↑↑ thrombus formation # EHC-93: - at 4 h: ↔ TF ↑ thrombus formation - at 48 h: ↑↑ TF ↑↑ thrombus formation |
PM induced procoagulant activity in the lungs, via increased TF expression and aggravated thrombus formation. | [58] | ||
Hamsters (Pfd Gold) 100–110 g |
Intratracheal instillation of polystyrene particles: # 60 nm UFP -unmodified 500 μg/animal -carboxylated 500 μg/animal -amined 5, 50, 500 μg/animal # 400 nm: Amine-modified polystyrene particles 500 μg/animal Evaluation of BALF at 1 h after UFP exposure |
# Unmodified and carboxylated UFP: ↔ PMN influx # Amine-UFP (60 nm): ↑ PMN influx (50 and 500 µg/animal) ↑ protein, histamine (500 μg/animal) # Amine-particles (400 nm): ↑ PMN influx ↑ BALF protein ↔ BALF histamine |
# Unmodified and carboxylated UFP: ↔ thrombus formation # Amine-UFP (60 nm): ↑ thrombus formation (at 50 and 500 µg/animal) # Amine-particles (400 nm): ↔ thrombus formation |
Exposure to both positively charged UFP (60 & 400 nm) resulted in inflammation in the respiratory tract, but only the UFP (60 nm) rapidly activated the clotting system within an hour, leading to thrombosis. | [51] | |
Hamster 100–110 g |
Intratracheal instillation of polystyrene particles: # 60 nm UFP - unmodified 500 μg/animal - carboxylated 500 μg/animal - amined 5, 50, 500 μg/animal # 400 nm amined- polystyrene particles 500 μg/animal Evaluation of BALF at 1 h after UFP exposure |
# Unmodified and carboxylated UFP: ↔ PMN influx # Amine-particles (60 nm and 400 nm): ↑ PMN influx (50 μg) ↑↑ PMN influx (500 μg) |
# Unmodified and carboxylated UFP: ↔ thrombus formation # Amine-particles (60 nm): ↑↑ thrombus formation (50 μg) ↑ thrombus formation (500 μg) # Amine-particles (400 nm): ↔ thrombus formation |
UFP induced pulmonary inflammation and promoted thrombosis, but the degree of lung inflammation did not show a correlation with the extent of thrombosis. | [60] | |
Intratracheal instillation of DEP (SRM 1650) 5, 50, 500 μg/animal Evaluate at 1 h after UFP exposure |
BALF ↑ PMN influx ↑ protein ↑ histamine (at 50 and 500 μg/animal) |
↑ thrombus formation (50 μg) ↑↑ thrombus formation (500 μg) ↓ PFA100 closure time |
DEP exposure activated platelet and thrombin generation, leading to thrombosis. | |||
Female mice (C57BL/6) 8–10 wk-old sex-age-matched Sirt1 +/+ Sirt1 −/− Sirt1 overexpression in WT mice (vs. WT mice) |
Intranasal instillation of PM2.5 (SRM 8785) 100 µg/animal for 24 h |
# Sirt1 +/+: ↑ lung NF-ĸB ↑ BALF albumin, PMN ↑ BALF TNF-α & IL-6 # Sirt1 −/−: ↑↑ lung NF-κB ↑↑ BALF albumin, PMN ↑↑ BALF TNF-α & IL-6 |
# Sirt1 +/+: ↑ lung fibrin formation ↓ TFPI ↑ TF ↑ lung PAI-1 ↔ plasma PAI-1 ↓ lung TM # Sirt1 −/−: ↑ ↑ lung fibrin formation ↓ ↓ TFPI ↑ TF ↑ ↑ lung PAI-1 ↔ plasma PAI-1 ↓↓ lung TM # Sirt1 overexpression: ↓ lung fibrin formation ↑ lung TM |
PM2.5 exposure promoted pulmonary vascular injury and enhanced inflammation, coagulation, and inhibited fibrinolysis, which was regulated by Sirt1 and NF-κB pathways. | [53] | |
Male SD rats 8–12 wk-old |
Intratracheal instillation of PM2.5 once every 3 d for 30 d Doses: - Low dose: 1.8 mg/kg - Middle dose: 5.4 mg/kg - High dose: 16.2 mg/kg PM2.5 was collected from central Beijing, China |
↑ Alveolar wall thickening ↑ IL-6, IL-1β, CRP ↔ MCP-1 |
↓ Aortic valve peak blood flow ↑ thrombus formation ↑ TF ↑ TAT complexes ↑ Factor Xa ↑↑ D-dimer ↓ TM ↔ TFPI ↑ tPA ↓ vWF ↑ PT, PTT, TT ↔ fibrinogen ↑↑ ICAM-1, VCAM-1 |
↓ platelets | PM2.5 induced vascular endothelial injury, systemic inflammatory response, altered coagulation factors, anticoagulant pathway, and fibrinolytic system, resulting in the prothrombotic state, and DIC. | [54] |
Male Wistar Kyoto (WKY) rats 12–15 wk-old |
Intratracheal instillation of PM2.5 and PM10 from The Northern and Southern Mexico - Total fraction - Insoluble fraction - Soluble fraction (control) of each PM2.5 and PM10 3.3 mg/kg Evaluation at 24 or 72 h after PM exposure |
# Total fraction and insoluble fraction of PM2.5 & PM10: ↑ BALF cell count ↓ alveolar macrophages Lung tissue ↑ total protein, ↑ albumin, ↓ ascorbic acid ↑ MIP-2, TNF-α mRNA ↑ BALF MIP-2, TNF-α ↑ HO-1 ↑ LOX-1R, ↑ NOS |
# Total fraction and insoluble fraction of PM2.5 & PM10: ↑ lung TF mRNA ↓ tPA mRNA ↑ PAI-1 mRNA |
# Total fraction and insoluble fraction of PM2.5 & PM10: ↔ RBC, Hb, Hct, platelet, and WBC |
Exposure to PM aggravated pulmonary inflammation and oxidative stress, as well as disruption in the procoagulant and fibrinolytic pathways of the lung. | [55] |
Male mice (C57BL/6) 8–12 wk-old IL-6+/+ IL-6−/− IL-6+/+ depleted alveolar macrophages |
Intratracheal instillation of PM10 from ambient air in Düsseldorf, Germany 10 μg/animal for 24 h # Pretreated with Intratracheally instillation of liposomal clodronate 120 mg/animal for 48 h before PM exposure (Setting of WT mice depleted of alveolar macrophages) |
BALF # IL-6+/+ vs. non-PM10: ↑ macrophage, PMN ↑ IL-6, TNF-α, IFN-γ ↔ MCP-1, IL-10, IL-12 # IL-6−/− vs. non-PM10: ↑ macrophage, PMN ↔ IL-6 ↑ TNF-α ↔ MCP-1, IL-10, IL-12, IFN-γ # IL-6−/− vs. IL-6+/+: ↓ IL-6 ↔ TNF-α, MCP-1, IL-10, IL-12, IFN-γ # IL-6+/+ depleted alveolar macrophages: ↓ macrophage ↔ PMN ↓ IL-6 ↔ TNF-α, MCP-1, IL-10, IL-12, IFN-γ |
Plasma # IL-6+/+ vs. non-PM10: ↑ Factor II, VIII, X ↑ Fibrinogen ↓ Bleeding time ↓ PT, ↓ PTT ↓ thrombotic occlusion time ↑ TAT complexes # IL-6−/− vs. non-PM10: ↔ Factor VIII ↔ Bleeding time ↔ PT, ↔ PTT ↔ thrombotic occlusion time ↔TAT complexes # IL-6+/+ depleted alveolar macrophages: ↓ Factor VIII ↑ Bleeding time ↑ PT, ↑ PTT ↓ TAT complexes ↑ thrombotic occlusion time |
# IL-6+/+ vs. non-PM10: ↑ Platelet # IL-6−/− vs. non-PM10: ↔ Platelet # IL-6+/+ depleted alveolar macrophages: ↓ Platelet |
PM10 exposure-induced pulmonary inflammation, and IL-6 release. IL-6 was the key mediator, which enhanced coagulation factor function, resulted in shortening of clotting time, and led to thrombosis. Blocking either the macrophage function or IL-6 signal could alleviate PM-induced prothrombotic state. |
[52] |
This entry is adapted from the peer-reviewed paper 10.3390/ijerph19148771