title: Hyperoxia-induced hypertrophy and ion channel remodeling in left ventricle.
abstract: Ventricular arrhythmias account for high mortality in cardiopulmonary patients in intensive care units. Cardiovascular alterations and molecular-level changes in response to the commonly used oxygen treatment remains unknown. In the present study we investigated cardiac hypertrophy and cardiac complications in mice subjected to hyperoxia. Results demonstrate that there is a significant increase in average heart weight to tibia length (22%) in mice subjected to hyperoxia treatment vs. normoxia. Functional assessment was performed in mice subjected to hyperoxic treatment, and results demonstrate impaired cardiac function with decreased cardiac output and heart rate. Staining of transverse cardiac sections clearly demonstrates an increase in the cross-sectional area from hyperoxic hearts compared with control hearts. Quantitative real-time RT-PCR and Western blot analysis indicated differential mRNA and protein expression levels between hyperoxia-treated and control left ventricles for ion channels including Kv4.2 (-2 ± 0.08), Kv2.1 (2.54 ± 0.48), and Scn5a (1.4 ± 0.07); chaperone KChIP2 (-1.7 ± 0.06); transcriptional factors such as GATA4 (-1.5 ± 0.05), Irx5 (5.6 ± 1.74), NFκB1 (4.17 ± 0.43); hypertrophy markers including MHC-6 (2.17 ± 0.36) and MHC-7 (4.62 ± 0.76); gap junction protein Gja1 (4.4 ± 0.8); and microRNA processing enzyme Drosha (4.6 ± 0.58). Taken together, the data presented here clearly indicate that hyperoxia induces left ventricular remodeling and hypertrophy and alters the expression of Kv4.2 and MHC6/7 in the heart.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Siva K
authors.initials: SK
authors.lastname: Panguluri
authors.forename: Jared
authors.initials: J
authors.lastname: Tur
authors.forename: Jutaro
authors.initials: J
authors.lastname: Fukumoto
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Sneed
authors.forename: Narasaiah
authors.initials: N
authors.lastname: Kolliputi
authors.forename: Eric S
authors.initials: ES
authors.lastname: Bennett
authors.forename: Srinivas M
authors.initials: SM
authors.lastname: Tipparaju
mesh_terms: D000818:Animals; D002302:Cardiac Output; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D006339:Heart Rate; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D018496:Hyperoxia / Q000150:complications*; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D051669:Shab Potassium Channels / Q000235:genetics / Q000378:metabolism; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014463:Ultrasonography
chemical_list: D018031:Connexin 43; C543076:GJA1 protein, mouse; C496755:Kcnip2 protein, mouse; D051605:Kv Channel-Interacting Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568321:Scn5a protein, mouse; D051669:Shab Potassium Channels; D051672:Shal Potassium Channels; D014157:Transcription Factors; C513400:Drosha protein, mouse; D043244:Ribonuclease III; D018995:Myosin Heavy Chains
keywords: heart; hyperoxia; hypertrophy; ion channel regulation; potassium channel; redox