title: Airborne fine particulate matter alters the expression of endothelin receptors in rat coronary arteries.
abstract: Exposure to airborne fine particulate matter (PM2.5) is associated with cardiovascular diseases. However, a comprehensive understanding of the underlying mechanisms by which PM2.5induces or aggravates these diseases is still insufficiently clear. The present study investigated whether PM2.5alters the expression of the endothelin subtype B (ETB) and endothelin subtype A (ETA) receptors in the coronary artery and examined the underlying mechanisms. Rat coronary artery segments were cultured with PM2.5in the presence or absence of MEK/ERK1/2, JNK, and p38 pathway inhibitors. Contractile reactivity was measured by myography. ETBand ETAreceptor expression was evaluated using RT-PCR, western blot and immunohistochemistry. Compared with fresh arteries, the cultured coronary arteries showed a significantly enhanced contraction mediated by the ETBreceptor and an unaltered contraction mediated by the ETAreceptor. Culture with PM2.5significantly enhanced the contraction and the mRNA and protein expression levels of the ETBand ETAreceptors in the coronary arteries, suggesting that PM2.5induces an upregulation of ETAand ETBreceptors. In addition, the PM2.5-induced increases in ETB- and ETA-mediated vasoconstriction and receptor expressions could be notably decreased by MEK1/2 inhibitor, U0126 and Raf inhibitor, SB386023, suggesting that the upregulation of ETBand ETAreceptors is related with MEK/ERK1/2 pathway. In conclusion, PM2.5induces the ETBand ETAreceptor upregulation in rat coronary arteries, and the MEK/ERK1/2 pathway may be involved in this process.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Environmental Science and Engineering, Xi'an Jiaotong University, 28 Xianning West Road, Xi'an, 710049, China.
authors.forename: Zhen-Xing
authors.initials: ZX
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, China. Electronic address: yxy@xjtu.edu.cn.
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism*; D008297:Male; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D017466:Receptors, Endothelin
keywords: Coronary artery; Endothelin receptor; MAPK pathway; PM(2.5)