Table 3 Experimental studies in animals on PM exposure and HDL functionality
Author, year and country | Animal models | Number of included animals | Air pollutant | Exposure including route of exposure and level | Outcome | Results | Main findings |
|---|---|---|---|---|---|---|---|
Araujo et al. 2008, United States [31] | Male ApoE −/− mice (6 weeks) fed normal chow | Animals were randomly assigned to 3 groups: FA, PM2.5, UFP (n = 17/group) Controls exposed to FA: nE= 17 All: n = 51 | UFP (< 0,18 μm) or PM2.5 (< 2,5 μm) | UFP (112,61 μg/m3) or PM2.5 (438,29 μg/m3) or FA 5 h/day, 3-days/week, 75 h (40 days). Whole-body exposure chambers in a mobile laboratory located in downtown Los Angeles. | Atherosclerotic lesions HDL-C levels HDL anti-inflammatory properties Parameters of systemic inflammation and oxidative stress (malondialdehyde (MDA), lipid peroxidation, Nrf2-induced phase II enzyme expression, antioxidant phase II enzymes (catalase, glutathione S-transferase Ya and NAD(P)H-quinone oxidoreductase 1)) | Mice exposed to UFPs alone exhibited greater and more advanced lesions compared with FA- or PM2.5-exposed animals. Exposure to PM2.5 and UFP was associated with a decreased anti-inflammatory capacity of HDL (UFP greater than PM2.5), as well as increased hepatic MDA levels and Nrf2-regulated antioxidant genes. | Exposure to PM2.5 and UFP exhibited the development of dysfunctional HDL (decreased anti-inflammatory capacity) without affecting HDL-C levels. |
Li et al. 2013, United States [32] | Male LDLR −/− mice on a high-fat diet | Controls exposed to FA: n = 5 All: n = 15 | UFP (< 0,10–0,20 μm) | UFP (360 μg/m3) or FA for 5 h/day, 3-days/week for 10 weeks. The collection of UFPs was conducted in urban regions of Los Angeles, and animals were exposed in whole-body chambers. | Atherosclerotic lesions HDL-C level HDL antioxidative capacity (HDL oxidation index (HOI)) Paraoxonase (PON) activity Parameters of systemic inflammation and oxidative stress (hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs) serum amyloid A (SAA), tumor necrosis factor (TNF-α)) | UFP exposure was associated with a greater atherosclerotic lesion size compared with FA-exposed animals. Mice exposed to UFPs developed a reduced plasma HDL-C level, PON activity, and HDL antioxidant capacity; but increased LDL oxidation, free oxidized fatty acids, triglycerides, SAA and TNF-α, accompanied by an increase in atherosclerotic lesion size. | Exposure to UFP was associated with reduced HDL antioxidant capacity, PON activity as well as HDL-C levels. |
Yin et al. 2013, United States [33] | Male ApoE −/− mice (9 weeks) | Mice were assigned to 3 groups: DE, FA, DE + FA (n = 12–13/group) Controls exposed to FA: n = 13 All: n = 38 | Diesel exhaust (DE) of PM2.5 | DE at ≈250 μg/m3of PM2.5 or FA for 2 weeks. DE was generated in the exposure facility and animals were exposed in whole-body chambers. | HDL-C HDL anti-inflammatory capacity HDL antioxidative capacity Paraoxonase (PON) activity Myeloperoxidase (MPO) Malondialdehyde (MDA) Hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs) | Exposure to DE led to systemic pro-oxidative effects characterized by increased lipid peroxidation and alteration of HDL protective capacities. DE effects on HDL antioxidant capacity were negatively correlated with PON activity, but positively correlated with levels of plasma 8-isoprostanes, 12-HETEs, 13-HODEs, liver MDA, and accompanied by perturbed HDL anti-inflammatory capacity and activation of the 5-lipoxygenase pathway in the liver. PON1 activity was significantly reduced among the DE-exposed mice compared to the FA group. No significant association was found with MPO. | DE exposure induced generation of dysfunctional pro-oxidative HDL, without affecting HDL-C levels. Several markers of lipid peroxidation in the blood and liver strongly correlated with the degree of HDL dysfunction. |
Feng et al. 2019, China [34] | Male Wistar rats (6 weeks) | Rats were divided into 4 groups (8/group) by exercise status (sedentary vs. exercised) and PM2.5 exposure (instilled vs. non-instilled). All: n = 32 | PM2.5 | PM2.5 (3 mg/kg) on day 1, 3 and 5 in week 7. PM2.5 sample was collected in Beijing, China. Rats were exposed via intratracheal installation. | HDL-C level HDL cholesterol efflux capacity (CEC) HDL oxidization index (HDL-OI) | The levels of HDL-C, HDL-CEC and HDL-OI showed no significant changes between instilled vs. non-instilled rats, indicating that PM2.5 instillation did not significantly alter HDL function. | PM2.5 instillation showed limited adverse impact on HDL function (CEC, HOI), including HDL-C level. |