title: Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis.
abstract: Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0.05) decreased renal and cardiac expression of the antifibrotic microRNA miR-29b-3 and increased expression of molecular fibrosis markers. In terms of cardiac and renal organ structure and function, exposure to cigarette smoke led to significantly increased systolic blood pressure, cardiac hypertrophy, cardiac and renal fibrosis, and decreased renal function. These data indicate that decreased expression of miR-29b-3p is a novel mechanism wherein cigarette smoke promotes accelerated cardiac and renal tissue injury in CKD. (155 words).
authors: College of Medicine and Life Sciences, Department of Medicine, Division of Cardiovascular Medicine and Center for Hypertension and Personalized Medicine, University of Toledo, Toledo, Ohio; cdrummo88@gmail.com.
authors: Christopher A
authors: 0000-0002-0378-9882
authors: CA
authors: Drummond
authors: Pulmonary Critical Care Section, Veterans Affairs San Diego Healthcare System and Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego Health Sciences, San Diego, California; and.
authors: Laura E
authors: 0000-0002-5091-2660
authors: LE
authors: Crotty Alexander
authors: College of Medicine and Life Sciences, Department of Medicine, Division of Cardiovascular Medicine and Center for Hypertension and Personalized Medicine, University of Toledo, Toledo, Ohio.
authors: Steven T
authors: ST
authors: Haller
authors: College of Medicine and Life Sciences, Department of Medicine, Division of Cardiovascular Medicine and Center for Hypertension and Personalized Medicine, University of Toledo, Toledo, Ohio.
authors: Xiaoming
authors: X
authors: Fan
authors: College of Medicine and Life Sciences, Department of Medicine, Division of Cardiovascular Medicine and Center for Hypertension and Personalized Medicine, University of Toledo, Toledo, Ohio.
authors: Jeffrey X
authors: JX
authors: Xie
authors: College of Medicine and Life Sciences, Department of Medicine, Division of Cardiovascular Medicine and Center for Hypertension and Personalized Medicine, University of Toledo, Toledo, Ohio.
authors: David J
authors: DJ
authors: Kennedy
authors: Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia.
authors: Jiang
authors: J
authors: Liu
authors: Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia.
authors: Yanling
authors: Y
authors: Yan
authors: Division of Pulmonary Medicine (Critical Care and Sleep Medicine), University of Toledo, Toledo, Ohio.
authors: Dawn-Alita
authors: DA
authors: Hernandez
authors: Pulmonary Critical Care Section, Veterans Affairs San Diego Healthcare System and Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego Health Sciences, San Diego, California; and.
authors: Denzil P
authors: DP
authors: Mathew
authors: College of Medicine and Life Sciences, Department of Medicine, Division of Cardiovascular Medicine and Center for Hypertension and Personalized Medicine, University of Toledo, Toledo, Ohio.
authors: Christopher J
authors: CJ
authors: Cooper
authors: Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia.
authors: Joseph I
authors: JI
authors: Shapiro
authors: College of Medicine and Life Sciences, Department of Medicine, Division of Cardiovascular Medicine and Center for Hypertension and Personalized Medicine, University of Toledo, Toledo, Ohio.
authors: Jiang
authors: J
authors: Tian
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D000073865:Cigarette Smoking / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005355:Fibrosis / Q000235:genetics*; D006321:Heart / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000235:genetics
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: combustible cigarettes; fibrosis; microRNA; physiology; tobacco-related disease; toxicology