Sex-based differences in myocardial infarction-induced kidney damage following cigarette smoking exposure: more renal protection in premenopausal female mice

Biosci Rep. 2020 Jun 26;40(6):BSR20193229. doi: 10.1042/BSR20193229.

Abstract

The impact of cigarette smoking (CS) on kidney homeostasis in the presence of myocardial infarction (MI) in both males and females remains poorly elucidated. C57BL6/J mice were exposed to 2 weeks of CS prior to MI induction followed by 1 week of CS exposure in order to investigate the impact of CS on kidney damage in the presence of MI. Cardiac hemodynamic analysis revealed a significant decrease in ejection fraction (EF) in CS-exposed MI male mice when compared with the relative female subjects, whereas cardiac output (CO) comparably decreased in CS-exposed MI mice of both sexes. Kidney structural alterations, including glomerular retraction, proximal convoluted tubule (PCT) cross-sectional area, and total renal fibrosis were more pronounced in CS-exposed MI male mice when compared with the relative female group. Although renal reactive oxygen species (ROS) generation and glomerular DNA fragmentation significantly increased to the same extent in CS-exposed MI mice of both sexes, alpha-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) significantly increased in CS-exposed MI male mice, only. Metabolically, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide riboside-1 (NMRK-1) substantially increased in CS-exposed MI female mice only, whereas sirtuin (SIRT)-1 and SIRT-3 substantially decreased in CS-exposed MI male mice compared with their relative female group. Additionally, renal NAD levels significantly decreased only in CS-exposed MI male mice. In conclusion, MI female mice exhibited pronounced renal protection following CS when compared with the relative male groups.

Keywords: Cigarette smoking; Kidney damage; Myocardial infarction; gender differences.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • DNA Damage
  • Disease Models, Animal
  • Female
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Male
  • Mice, Inbred C57BL
  • Myocardial Infarction / complications*
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Premenopause*
  • Reactive Oxygen Species / metabolism
  • Sex Factors
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism
  • Smoke*
  • Tobacco Products*

Substances

  • Actins
  • CCN2 protein, mouse
  • Cytokines
  • Reactive Oxygen Species
  • Sirt3 protein, mouse
  • Smoke
  • alpha-smooth muscle actin, mouse
  • Connective Tissue Growth Factor
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, mouse
  • Phosphotransferases (Alcohol Group Acceptor)
  • Nmrk1 protein, mouse
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Sirtuin 3