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

Nada J Habeichi,Hiam Al-Awassi,Cynthia Tannous,Ali Mroueh,Ahmad Husari,Rana Ghali,Raffaele Altara,Fouad A Zouein,George W Booz,Ahmed El-Yazbi,Abdullah Kaplan,Abdo Jurjus

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.

Highlights

Cardiovascular diseases (CVDs) remain the leading cause of death in males and females worldwide [1,2]
cigarette smoking (CS)-exposed mice of both sexes showed no significant change in ejection fraction (EF) when compared with their relative non-exposed groups, whereas myocardial infarction (MI) mice of both sexes experienced a substantial decrease in EF when compared with non-exposed and CS-exposed groups
No significant difference between control male and female mice was observed (Figure 1A)

Summary

Introduction

Cardiovascular diseases (CVDs) remain the leading cause of death in males and females worldwide [1,2]. The World Health Organization (WHO) estimates that more than 17 million CVD deaths annually are due to ischemic heart diseases, involving mostly myocardial infarction (MI) and strokes [3]. The male to female MI risk ratio under 45 years of age is 10:1, while dropping substantially in those over 75 years of age to 2:1 [7]. Patients diagnosed with MI are at high risk of heart failure development, and of multiple comorbidities including a 29-fold increase in acute kidney injury (AKI) through the cardio-renal interrelationship [8,9]. Diabetes mellitus, and cigarette smoking (CS) are identified as high risk factors for both MI and AKI development [13]

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Discussion

Conclusion