title: Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension.
abstract: Cerium oxide (CeO2) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO2 nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO2 nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO2 groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO2 nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO2 nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, β-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO2 nanoparticle administration may attenuate the hypertrophic response of the heart following PAH.
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, United States; Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, United States.
authors.forename: Madhukar B
authors.initials: MB
authors.lastname: Kolli
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, United States; Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, United States.
authors.forename: Nandini D P K
authors.initials: NDPK
authors.lastname: Manne
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, United States.
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Para
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, United States; Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, United States.
authors.forename: Siva K
authors.initials: SK
authors.lastname: Nalabotu
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, United States.
authors.forename: Geeta
authors.initials: G
authors.lastname: Nandyala
authors.affiliation: Department of Mechanical Engineering and Engineering Mechanics, Michigan Technological University, Houghton, MI, United States.
authors.forename: Tolou
authors.initials: T
authors.lastname: Shokuhfar
authors.affiliation: Department of Mechanical Engineering and Engineering Mechanics, Michigan Technological University, Houghton, MI, United States; School of Materials Science and Engineering, Shandong University, Ji'nan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Mechanical Engineering and Engineering Mechanics, Michigan Technological University, Houghton, MI, United States.
authors.forename: Azhang
authors.initials: A
authors.lastname: Hamlekhan
authors.affiliation: Health Effects Laboratory Division, NIOSH, Morgantown, WV, United States.
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United States.
authors.forename: Paulette S
authors.initials: PS
authors.lastname: Wehner
authors.affiliation: Department of Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United States.
authors.forename: Lucy
authors.initials: L
authors.lastname: Dornon
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, United States.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Arvapalli
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, United States.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, United States; Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, United States; Department of Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United States; Department of Pharmaceutical Sciences and Research, Marshall University, Huntington, WV, United States. Electronic address: blough@marshall.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002563:Cerium / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000150:complications*; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D053758:Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D002563:Cerium; C030583:ceric oxide; D016686:Monocrotaline
keywords: Cerium oxide nanoparticles; Monocrotaline; Pulmonary arterial hypertension; Right ventricular hypertrophy