title: Alpha B-crystallin prevents the arrhythmogenic effects of particulate matter isolated from ambient air by attenuating oxidative stress.
abstract: Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated by particulate matter (PM) isolated from ambient air and linked to prolonged repolarization and cardiac arrhythmia. We evaluated whether alpha B-crystallin (CryAB), a heat shock protein, could prevent the arrhythmogenic effects of PM by preventing CaMKII activation. CryAB was delivered into cardiac cells using a TAT-protein transduction domain (TAT-CryAB). ECGs were measured before and after tracheal exposure of diesel exhaust particles (DEP) and each intervention in adult Sprague-Dawley rats. After endotracheal exposure of DEP (200 μg/mL for 30 minutes, n=11), QT intervals were prolonged from 115±14 ms to 144±20 ms (p=0.03), and premature ventricular contractions were observed more frequently (0% vs. 44%) than control (n=5) and TAT-Cry (n=5). However, DEP-induced arrhythmia was not observed in TAT-CryAB (1 mg/kg) pretreated rats (n=5). In optical mapping of Langendorff-perfused rat heats, compared with baseline, DEP infusion of 12.5 μg/mL (n=12) increased apicobasal action potential duration (APD) differences from 2±6 ms to 36±15 ms (p<0.001), APD restitution slope from 0.26±0.07 to 1.19±0.11 (p<0.001) and ventricular tachycardia (VT) from 0% to 75% (p<0.001). DEP infusion easily induced spatially discordant alternans. However, the effects of DEP were prevented by TAT-CryAB (1mg/kg, n=9). In rat myocytes, while DEP increased reactive oxygen species (ROS) generation and phosphated CaMKII, TAT-CryAB prevented these effects. In conclusion, CryAB, a small heat shock protein, might prevent the arrhythmogenic effects of PM by attenuating ROS generation and CaMKII activation.
authors.affiliation: The Division of Cardiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyelim
authors.initials: H
authors.lastname: Park
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Park
authors.forename: Hyunju
authors.initials: H
authors.lastname: Jeon
authors.forename: Byeong-Wook
authors.initials: BW
authors.lastname: Song
authors.forename: Jin-Bae
authors.initials: JB
authors.lastname: Kim
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Hui-Nam
authors.initials: HN
authors.lastname: Pak
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
authors.forename: Moon-Hyoung
authors.initials: MH
authors.lastname: Lee
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Chung
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
mesh_terms: D000200:Action Potentials; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity; D018879:Ventricular Premature Complexes / Q000139:chemically induced / Q000517:prevention & control; D038203:alpha-Crystallin B Chain / Q000008:administration & dosage / Q000502:physiology*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D038203:alpha-Crystallin B Chain; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2