The impact of cigarette smoking on Type I Cardio-Renal Syndrome in Male and Female Mice

Abstract

Overwhelming epidemiological evidence correlates cardiovascular diseases (CVDs) with acute kidney injury (AKI) and cigarette smoking (CS). CS contains thousands of carcinogenic and non-carcinogenic chemicals that play a key role in reducing cell viability in renal proximal tubular epithelial cells through acute or chronic pathological mechanisms. Myocardial infarction (MI) is a major public health concern and a leading cause of type I cardio-renal syndrome in both males and females. In this study, the impact of CS on type I cardio-renal syndrome in both genders was investigated in a mouse model of MI using 3 groups: control, MI, and MI + CS of each gender. Histological analysis of MI+CS groups showed morphological alterations in the kidneys including glomerular retraction, proximal convoluted tubule dilatation, and interstitial fibrosis, which were significantly heightened in males when compared to the relative female subjects. Molecularly, the pro-inflammatory cytokine IL-1β was markedly increased in males post MI+CS when compared to the control group, whereas, the anti- inflammatory cytokine IL-13 was significantly heightened in females MI following CS exposure when compared to the relative male group. The pro-fibrotic biomarkers MMP8 and α-SMA were markedly increased in MI males following CS exposure when compared to the relative female group. Of note, MMP13, CTGF tended to be non- significantly higher in MI males following CS exposure when compared to relative female mice despite a comparable increase in ROS production and DNA fragmentation. Metabolically, NAMPT and NMRK1 were significantly increased in MI females following CS exposure when compared to relative male mice. Both SIRT1 and SIRT3 were markedly decreased in MI male following CS exposure when compared to the relative female subjects. Additionally, PARP-1 tended to be higher in MI male group following CS exposure when compared to the relative female group. Last but not least, NAD levels significantly decreased in MI male mice follow