Chronic Electronic Cigarette Vapor Inhalation Induces Renal Injury and Functional Decline in Female Mice

Abstract

Clinical studies indicate that combustible cigarette smoke increases renal and cardiac tissue injury progression and functional decline in the setting of chronic kidney disease (CKD). Novel nicotine delivery devices like electronic (e)‐cigarettes are used by over 10% of the population and produce vapor which may also induce renal injury. To establish whether e‐cigarette vapor inhalation induced renal injury in the form of fibrosis and decreased renal injury our current study utilized a nose‐only inhalation exposure system to induce 8 week‐old female mice to inhale e‐cigarette vapor containing 24mg/mL of nicotine suspended in a solution of 50% propylene glycol and 50% vegetable glycerin using the following parameters: 12 seconds of vapor exposure every 60 seconds for 60 minutes five days per week for 1‐, 3‐ and 6‐months. Following e‐cigarette exposure, assessment of renal fibrosis, glomerular filtration rate, and expression of the antifibrotic microRNA miR‐29b‐3p were evaluated. Mice exposed to e‐cigarette vapor suffered a 31% decline in renal tissue expression of miR‐29b‐3p vs air‐exposed controls (p<0.05). Additionally, mRNA targets of miR‐29b‐3p that regulate fibrosis formation or are part of fibrosis were also significantly increased in the kidneys of e‐cigarette exposed mice versus air controls, i.e., Collagen 1A1 (increased 98%; p<0.05); Collagen 3A1 (129% increase; p<0.05); Collagen 4a1 (72% increase; p<0.05); Integrin beta 1 (58% increase; p<0.05); and Fibrillin 1 (100% increase; p<0.05). Additionally, we observed a significant increase in renal fibrosis at the 3‐ and 6‐month time points as assessed by Trichrome staining in these animals. Lastly, following 3‐months of exposure to e‐cigarette vapor renal function was significantly reduced by 21% versus air exposed controls (p=0.017). These data are the first to indicate that e‐cigarettes induce renal fibrosis and functional decline. In addition, these data suggest a novel miR‐29b‐3p mediated mechanism linking e‐cigarette vapor exposure and renal injury and functional decline.Support or Funding InformationThis work was supported by the National Institutes of Health (1F32DK104615‐01 to CAD and HL‐105649 to JT. Additional support was from a Veterans Affairs BLR&D Career Development Award (1IK2BX001313 to LCA), AHA Beginning Grant‐in‐aid (16BGIA27790079 to LCA), and O'Brien Center Daniel O'Connor Memorial Pilot Award to LCA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.