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Nasal Administration of Diesel Exhaust Particles Does Not Evoke Dysfunction or Initiate Autophagy in Murine Femoral Arteries
Author(s) -
Cho Jaemin,
Kim JiSeok,
Lewis Joshua B,
Reynolds Paul R,
Bikman Benjamin,
Symons J David
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.840.26
Subject(s) - phenylephrine , chemistry , reactive oxygen species , nitric oxide , lung , autophagy , diesel exhaust , inhalation , medicine , endocrinology , pharmacology , immunology , anesthesia , diesel fuel , biochemistry , blood pressure , apoptosis , organic chemistry
Fine particulate matter (PM 2.5 ) from air pollution is associated with cardiovascular morbidity and mortality. Combusted diesel exhaust emissions are the major source of PM 2.5 . Upon inhalation of diesel exhaust particles (DEPs), an inflammatory response in the lung could release prothrombotic and inflammatory cytokines into the circulation. In addition, the nanometer size of DEP has potential to allow transportation to and translocation across the respiratory epithelium and into the circulation. In both cases, DEP could act on perfusion territories that are distal to the lung and evoke dysfunction. Recent reports indicate that impaired endothelial cell nitric oxide (NO) bioavailability upon exposure to DEPs might be secondary to exaggerated reactive oxygen species (ROS) generation. ROS are known activators of autophagy in a number of cell types. We hypothesized that exposure to DEPs evokes dysfunction and initiates autophagy in murine femoral arteries. Four‐month old female C57Bl6 mice received 10 exposures to 0 ng (CON, n=5) or 35 ng diesel exhaust particles (DEP, n=5) over 14 days via a nose‐only nebulization unit. After the last treatment arteries were prepared to assess autophagy‐related protein expression via immunoblotting, or vascular reactivity via isometric tension procedures. Internal diameter (180 ± 9 and 190 ± 13 μm) and L max tension (738 ± 10 and 731 ± 38 mg) was similar in femoral arteries (n=5 per group) from CON and DEP animals, respectively. Tension development to potassium chloride (KCL; 10–100 mM) and phenylephrine (PE, 10 −8 –10 −5 M) was similar between groups, indicating that non‐receptor mediated and receptor‐mediated vasocontractile mechanisms, respectively, were intact. After precontraction using PE, relaxation to the endothelium‐dependent vasodilator acetylcholine (ACh; 10 −8 –10 −6 M), and the endothelium‐independent vasodilator sodium nitroprusside (SNP, 10 −9 –10 −4 M), was similar between groups. Indices of autophagy were assessed in homogenates of aorta and iliac artery from the same animals. Autophagy related gene 3 (Atg3) is the phosphatidylethanolamine‐transferase that performs the final lipid‐conjugation modification of Atg8 (LC3) required for its association with phagophore membranes i.e., completes the conversion of LC3I to LC3II. LC3II:GAPDH, LC3II:LC3I, Atg3:GAPDH, and Atg7:GAPDH were similar in homogenates from CON and DEP animals. At least in the context of our experimental conditions, exposure to DEPs does not alter femoral artery function or arterial (aorta/iliac artery) autophagy.